title: Demon Hunter

text: Demon Hunter returned to the studio to record their second full-length release, "Summer of Darkness", with McCaddon contributing, and again with Jesse drumming. "Summer of Darkness" hit stores on May 4, 2004, and was a modest success, propelling Demon Hunter into the secular scene, with the addition of the music video "Not Ready to Die" on MTV2's "Headbangers Ball" and Fuse TV, along with single "My Heartstrings Come Undone" being placed on the "" soundtrack. The album featured four guest vocal appearances, including Mike Williams of The Agony Scene on "Beheaded", Brock Lindow of 36 Crazyfists on "Beauty Through The Eyes of a Predator", Howard Jones from Killswitch Engage on "Our Faces Fall Apart" and Trevor McNevan of Thousand Foot Krutch on "Coffin Builder".


title: Demon Hunter

text: Demon Hunter hit the road that summer with McCaddon on lead and Dunn on bass, and with new touring drummer Timothy "Yogi" Watts, as Jesse Sprinkle could not make the tour. This time Demon Hunter took with them rock/post-hardcore rookies Dead Poetic, along with metalcore band Haste the Day. Post-hardcore band Staple replaced Haste the Day towards the end of the tour.


title: Demon Hunter

text: In 2005, Demon Hunter went back to The Compound in Seattle, Washington to record their third album, entitled "The Triptych". The word "triptych" centers around the concept of three, as it was the band's third album. Included on the album is a cover of Prong's song "Snap Your Fingers, Snap Your Neck". This album debuted Watts as Sprinkle's permanent replacement on drums (Jesse having joined Dead Poetic) as well as the addition of Ethan Luck as lead guitarist, replacing Kris McCaddon. "The Triptych" was even bigger than "Summer of Darkness", selling more than twice as many records on its first week of release than "Summer of Darkness" had. "Undying" was the band's first single from this album, and was also made into a music video directed by Chris Sims.


title: Demon Hunter

text: Demon Hunter's only 2006 tour took place over the summer with Zao, Becoming the Archetype, August Burns Red, and Spoken. The band shot a video for "One Thousand Apologies" after the tour was over, with director Darren Doane at the helm. "The Triptych" was re-released on October 31, 2006, with a DVD accompanying the album, and four extra songs added to the original album.


title: Demon Hunter

text: The hard rock and heavy metal based magazine, "Revolver", published a cover story on Christian metal in December 2006, featuring what the magazine called "The Holy Alliance": Spencer Chamberlain from Underoath, Ryan Clark from Demon Hunter, Tim Lambesis from As I Lay Dying, and Cory Brandan Putman from Norma Jean.


title: Demon Hunter

text: Demon Hunter entered the studio in June 2007 to record their fourth full-length album, "Storm the Gates of Hell", which was released on November 6, 2007. Solid State released three versions of the album with various bonuses. "Fading Away" was the album's first single and music video. In spite of the bands secular popularity, they continued to support the underground Christian metal scene by appearing on obscure radio programs such as The Full Armor of God Broadcast in January 2008. On March 13, 2008, "Carry Me Down" debuted on "Headbangers Ball"s website as the album's second music video, and made its television premiere on March 15 on the same show.


title: Demon Hunter

text: In 2008, the band headlined the "Stronger Than Hell" tour, which started May 26 in Seattle, Washington. The tour featured the recently reunited Christian metal forefathers Living Sacrifice, whose lead singer Bruce Fitzhugh was featured as a guest vocalist on "Storm the Gates of Hell"s track titled "Sixteen". The tour also included Oh, Sleeper, The Famine, and Advent. This tour completed July 5, 2008, at Cornerstone Festival in Illinois. Demon Hunter released "45 Days" in November, a box set comprising two DVDs and a CD containing a documentary film about the band and their fans, a pro-shot performance from the "Stronger Than Hell" tour and a brand new score written exclusively for the film along with two bonus tracks. "45 Days" was directed by Cale Glendening.


title: Demon Hunter

text: A live album, "Live in Nashville", was released on January 27, 2009. It includes 14 songs from their show in Nashville, Tennessee, from their "Stronger Than Hell" tour. The album features The Showdown lead guitarist Patrick Judge, who filled in for Luck on several of the "Stronger Than Hell" dates due to Luck's conflicting scheduling commitments as drummer for Relient K.


title: Demon Hunter

text: Judge also filled in for Brian Leppke of metalcore band Bleeding Through when he was unable to turn up for the Thrash and Burn tour in May.


title: Demon Hunter

text: In 2009, Don Clark left the band to pursue his graphic designer career, and to be with his family. Ethan Luck also left, as he could not keep up with the hectic schedule of being in both Demon Hunter and Relient K. On August 28, Demon Hunter released an official statement with a new band photograph, stating that Patrick Judge was the new, permanent replacement for Luck. However, the statement made no mention of Randy Torres's joining the band; a new band photograph included him as well. An official replacement for Don Clark was announced in Demon Hunter's exclusive fan club, The Blessed Resistance, with the announcement of Ryan Helm, formerly of The Ascendicate, as the band's new permanent rhythm guitarist.


title: Demon Hunter

text: The band released "The World Is a Thorn" on March 9, 2010. It featured guest vocals by Dave Peters of Throwdown in "Feel As Though You Could", Christian Älvestam of Miseration in "Just Breathe", and Björn "Speed" Strid of Soilwork featured in the single "Collapsing". The album debuted at No. 39 on the "Billboard" 200 with first-week sales of 14,000.


title: Demon Hunter

text: The band joined As I Lay Dying on tour in March, marking the first time Demon Hunter ever toured as a supporting act, rather than the headliner. Blessthefall and War of Ages were also on the bill. Demon Hunter released an anthology of their first three albums on March 8, 2011, titled "Death, a Destination". In December 2011, Ryan Helm announced that he would be leaving Demon Hunter to concentrate on his solo project, Damien Deadson. Helm stated that the departure, "was inevitable; however, it was on good terms."


title: Demon Hunter

text: In January 2012, it was announced on the Solid State Records website that Jeremiah Scott, bassist for The Showdown, had joined the band in the position of rhythm guitar.


title: Demon Hunter

text: Their sixth album, "True Defiance", released April 10, 2012, was a commercial success, reaching No. 36 on the "Billboard" 200 and No. 2 on the Top Christian Albums chart and received generally positive to mixed reviews. A month before the album was released, Demon Hunter released the song "My Destiny" as the first official single from the album and released "Someone to Hate" and "Dead Flowers" as promotional singles. The band also released a deluxe edition of the album that included two bonus songs, "What is Left" and "I Am a Stone".


title: Demon Hunter

text: In July 2012, the band toured for the album along with Bleeding Through, Cancer Bats, and The Plot in You. Not long after, they also announced a tour in the countries of Brazil, Argentina, and Colombia in South America. The band was part of a tour called "Another Year Another Tour", their first tour of 2013, alongside headline act In Flames, as well two other bands, All Shall Perish, and Battlecross.


title: Demon Hunter

text: Demon Hunter began releasing teaser posts on January 30, 2014 related to "Extremist", which was released on March 18, 2014. Demon Hunter released the album's first single, "Artificial Light", on their YouTube account February 13, 2014, and also released websites to pre-order their new album. "The Last One Alive", and "I Will Fail You" were eventually released as promotional singles shortly after. "Extremist" debuted at No. 16 on the "Billboard" 200 selling approximately 18,000 copies in the first week of release. This is the band's highest chart debut, being 20 steps higher than their highly regarded previous effort, "True Defiance" which debuted at No. 36.


title: Demon Hunter

text: In August 2014, the band went on a brief tour with Alternative metal band, Red, and the more Alternative rock band, Veridia.


title: Demon Hunter

text: Demon Hunter officially released their eighth studio album, "Outlive", on Solid State Records on March 31, 2017. In December 2016, they released the first single for "Outlive": "Cold Winter Sun". On February 15, 2017, they announced that a music video for their second single "Died In My Sleep" would be released.


title: Demon Hunter

text: On December 3, 2018 they announced two albums—"War" and "Peace"—were scheduled to be released in March 2019. Demon Hunter released both albums on March 1, 2019. On March 16, 2019, the two albums made it into top 5 of the "Billboard" Christian Albums with "War" in the second place and "Peace" in the third place.


title: Demon Hunter

text: On November 10, 2020, the band announced their first acoustic album, "Songs of Death and Resurrection", which would feature acoustic renditions of songs such as "Dead Flowers" and "The Heart of a Graveyard", as well as featuring a new song, "Praise the Void", which would be released on March 5, 2021.


title: Demon Hunter

text: On December 15, 2021, it was announced that Richie Faulkner of Judas Priest recorded a guitar solo for the next album, "Exile", later announced for release in September 9, 2022, then delayed to October 28, 2022. The band quickly released three singles, “Freedom is Dead”, “Silence the World”, and “Defense Mechanism”, the latter two featuring Tom S. Englund (Evergrey) and Max Cavalera (ex-Sepultura, Soulfly) respectively, all released through their self-founded record label, Weapons MFG.


title: Demon Hunter

text: Demon Hunter started writing a follow-up album to "Exile" as early as October in 2022, shortly before their new album's release.


title: Demon Hunter

text: Don Clark stated, "I guess we liked to ride the fence. Then we got a little older, maybe wiser, and you know what, we're a Christian band. We're five dudes, we're all believers, we really don't want to ride the fence anymore." Ryan Clark claimed, "When we officially started we wanted to be very bold about it, we didn't see any purpose of just beating around the bush." Fans who are Christians are supportive of the band's bold faith position. "They respect that we don't walk the fence between a non-Christian and Christian band."


title: Demon Hunter

text: According to an "Esquire" interview, after Metallica requested that the US military stop using their music during interrogations in Iraq, Demon Hunter allegedly contacted the US military, offering their music as an alternative, which was accepted. A Navy SEAL who claimed to have killed Bin Laden was quoted as saying "'[W]e stopped using [Metallica's] music, and then a band called Demon Hunter got in touch and said, "We're all about promoting what you do." They sent us CDs and patches. I wore my Demon Hunter patch on every mission. I wore it when I blasted bin Laden.'" The day after the story broke, Demon Hunter addressed the situation by saying they approved US servicemen wearing their patch, but they didn't volunteer their music, nor did they have any knowledge of it being used for interrogations.


title: Amazon Spheres

text: The Amazon Spheres are three spherical conservatories comprising part of the Amazon headquarters campus in Seattle, Washington, United States. Designed by NBBJ and landscape firm Site Workshop, its three glass domes are covered in pentagonal hexecontahedron panels and serve as an employee lounge and workspace. The spheres, which range from three to four stories tall, house 40,000 plants, as well as meeting space and retail stores. They are located adjoining the Day 1 building on Lenora Street. The complex opened to Amazon employees and limited public access on January 30, 2018. The spheres are reserved mainly for Amazon employees, but are open to the public through weekly headquarters tours and an exhibit on the ground floor.


title: Amazon Spheres

text: The spheres are located along Lenora Street between 6th and 7th Avenues, under Day 1 in Amazon's Seattle headquarters campus. The three intersecting spherical domes range from in height and take up half of a city block. They use over 2,600 panes of glass and of steel, arranged with five-sided panels of a pentagonal hexecontahedron.


title: Amazon Spheres

text: The largest sphere, in the center, is four stories tall and has of space; it houses the cafeteria, stairway, elevators, and bathrooms. The stairwell shaft is covered by a four-story "living wall" with 25,000 plants, including carnivorous species from Asia. The spheres have meeting spaces, tables, and benches that can seat a total of 800 people.


title: Amazon Spheres

text: The complex, nicknamed "Bezos' balls" by the media, has become a recognizable landmark and tourist attraction for the Denny Triangle area since the beginning of its construction. The structure has been compared to the city's iconic Space Needle, built as a futuristic landmark for the Century 21 Exposition in 1962. It was designed with influences from biophilic design, incorporating nature into the built environment.


title: Amazon Spheres

text: The spheres have 40,000 plants from 50 countries and are divided into three areas, with the western and eastern domes segregated into the Old World and New World. The domes are kept at a temperature of and 60 percent humidity during the daytime. Amazon employed a full-time horticulturalist to grow the building's 40,000 plants over a three-year period at a greenhouse in Redmond. Amazon donated space in the greenhouse to the University of Washington's botany program during renovation of their Life Sciences Building in 2016. Among the 40 to 50 trees in the spheres, the largest is a "Ficus rubiginosa" tree, nicknamed "Rubi", which was lifted into the spheres by a crane in June 2017.


title: Amazon Spheres

text: An "Amorphophallus titanum" corpse flower named "Morticia" bloomed for 48 hours in October 2018, attracting 5,000 visitors to the Spheres as Amazon opened the facility to public viewing for a limited time. A taller corpse flower, named Bellatrix, bloomed in June 2019 and prompted another public viewing that attracted large crowds.


title: Amazon Spheres

text: Amazon began planning a large Seattle headquarters campus in the early 2010s, acquiring three blocks in the Denny Triangle area in 2012. The original design for the second tower included a six-story building with flexible workspaces and a meeting center, but was later changed to a spherical conservatory. The revised design by NBBJ, which had been in development since 2012, was unveiled in May 2013 to a mixed reaction from the city's project design review board. While hailed as a bold design, it was criticized for the lack of rain protection, public access, and the amount of energy needed to climatize the facility. In August, NBBJ released an updated design that replaced the supporting steel structures under the glass with organic forms called "Catalan spheres". The city's design review board approved the design in October 2013, after slight changes to the understructure were made.


title: Amazon Spheres

text: Construction on the spheres began in 2015, and the first pieces of the steel structure were erected in February 2016. The steel was painted white and covered with glass panels that were installed beginning in April. The first plant, an Australian tree fern, was moved from the Redmond greenhouse and planted in May 2017.


title: Amazon Spheres

text: The spheres were dedicated on January 29, 2018, by Jeff Bezos, Mayor Jenny Durkan, County Executive Dow Constantine, and Governor Jay Inslee. Bezos ceremonially opened the complex using an Alexa voice command. It opened to Amazon employees the following day, along with a public exhibit named the "Understory" below the spheres. Public access is provided as part of weekly guided tours of the Amazon headquarters campus and a twice-monthly weekend reservation program. They were temporarily closed to the public during the COVID-19 pandemic.


title: Giuseppe Rossi

text: Giuseppe Rossi (; born 1 February 1987) is a professional footballer who plays as a forward. Born in the United States, Rossi spent most of his career in Europe with Villarreal and Fiorentina, in addition to spells with other clubs in England, Italy and Spain, before returning to his country of birth to join Real Salt Lake for a single season in 2020.


title: Giuseppe Rossi

text: At international level, Rossi represented Italy at the 2008 Summer Olympics, and at the 2009 FIFA Confederations Cup, collecting 30 appearances and scoring seven goals at senior level between 2008 and 2014. Along with Mario Balotelli and Daniele De Rossi, he is Italy's all-time top scorer in the FIFA Confederations Cup, with 2 goals.


title: Giuseppe Rossi

text: Due to his prolific performances in the Spanish La Liga, Rossi earned the nickname "Pepito" Rossi, a reference to his namesake Paolo Rossi, who was nicknamed "Pablito" following his goalscoring performances in Italy's victorious 1982 FIFA World Cup campaign in Spain.


title: Giuseppe Rossi

text: Rossi is an Italian American, born to Italian immigrant parents in Teaneck, New Jersey. His father, Fernando Rossi from Fraine, Abruzzo, coached soccer and taught Italian and Spanish at Clifton High School. His mother, Cleonilde Rossi from Acquaviva d'Isernia, Molise, was also a language teacher at Clifton, and his sister, Tina, currently lives in the United States. Rossi played prep soccer at Clifton High School.


title: Giuseppe Rossi

text: After his father died in 2010, Rossi began to wear the number 49, which was the year of his father's birth. In 2014, he switched back to the number 22 jersey.


title: Giuseppe Rossi

text: When offered a spot on the youth team of Parma, Rossi (then 12) and his father moved to Italy until Manchester United bought his contract when he was 17. His first-team debut came on 20 November 2004, at home to Crystal Palace in the fifth round of the League Cup, as an 84th-minute substitute for David Bellion.


title: Giuseppe Rossi

text: For his Premier League debut on 15 October 2005, he came on in the 78th minute for Ruud van Nistelrooy and nine minutes later scored the last goal in a 3–1 win over Sunderland at the Stadium of Light. On 18 January 2006, in an FA Cup third-round replay, he started and scored twice as United beat non-league Burton Albion 5–0. Although Rossi did not play in the League Cup final against Wigan Athletic, Nemanja Vidić (who made a seven-minute cameo at the end of the game) gave Rossi his medal in recognition of Rossi's contribution to the team's success in the earlier rounds.


title: Giuseppe Rossi

text: At the start of the 2006–07 season, Rossi moved to Newcastle United on loan until 1 January 2007, where he was expected to gain some first team experience. He made his home debut on 24 September 2006. Rossi scored his only Newcastle goal in his first start on 25 October 2006, against Portsmouth in a League Cup third round tie at St James' Park.


title: Giuseppe Rossi

text: For the second half of the season, he was again loaned out, this time to his former club Parma, scoring nine goals in 19 league appearances.


title: Giuseppe Rossi

text: On 31 July 2007, Manchester United confirmed that Rossi had been sold to Spanish club Villarreal for an undisclosed fee, reportedly around £6.6 million (€10 million). He scored his first goal for Villarreal on his debut against Valencia on 26 August 2007.


title: Giuseppe Rossi

text: In his second season with Villarreal, Rossi had scored 12 goals in 30 league appearances, along with three goals in eight Champions League appearances. In January 2011, he signed a contract extension with Villarreal until 2016. The 2010–11 season proved to be his breakthrough season, as he scored 32 goals in 56 appearances in all competitions, helping the club to a fourth-place finish in La Liga, scoring 18 goals, which qualified them for the 2011–12 UEFA Champions League, also helping Villarreal to the semi-finals of the 2010–11 UEFA Europa League that season, scoring 11 goals, and the quarter-finals of the Copa del Rey. An anterior cruciate ligament injury on Rossi's right knee that he picked up in the 3–0 loss against Real Madrid on 26 October 2011 caused Rossi to be out for six months. Rossi re injured his anterior cruciate ligament of right knee in training on 13 April 2012, and was out for a further 10 months. At the end of his 6 year stay with Villarreal, he had scored 82 goals in 192 games in all competitions and became the club's all time top scorer. After 10 years of scoring his final goal for Villarreal in October 2011 in a match against Real Zaragoza, his record was surpassed by Gerard Moreno on 11 August 2021, after he scored a goal in the 2021 UEFA Super Cup match against Chelsea.


title: Giuseppe Rossi

text: On 4 January 2013, Fiorentina came to an agreement with Villarreal for the transfer of Rossi for a fee of approximately €11.8 million. On 7 January, Fiorentina held a press conference unveiling Rossi, where it was revealed the player had signed a four-year contract containing a €35 million release clause.


title: Giuseppe Rossi

text: On 21 May, the final day of the 2012–13 Serie A season, Rossi made his debut for Fiorentina as a substitute in a 5–1 win over Pescara.


title: Giuseppe Rossi

text: On 26 August, Rossi scored his first goal in 23 months in Fiorentina's opening match of the 2013–14 Serie A season – a 2–1 defeat of Catania. On 20 October, Rossi inspired Fiorentina to a 4–2 come from behind win over rivals Juventus, netting a 14-minute hat-trick that condemned Juve to their first defeat in Florence for 15 years.


title: Giuseppe Rossi

text: On 5 January 2014, Rossi was substituted in Fiorentina's match against Livorno as he suffered a second-degree sprain of his medial collateral ligament in his right knee. The blow was dealt by Leandro Rinaudo, who tackled Rossi from behind in a manner so dirty that he drew international condemnation. Up to this point Rossi had been the leading goal scorer in Serie A with 14 goals in 18 league appearances.


title: Giuseppe Rossi

text: Rossi returned from injury as a 69th-minute substitute in Fiorentina's 3–1 Coppa Italia final loss to Napoli on 3 May. On 6 May, he scored on his Serie A comeback – a 4–3 defeat to Sassuolo.


title: Giuseppe Rossi

text: On 14 August 2014, Rossi injured his medial meniscus of right knee in training. On 5 September 2014 Fiorentina confirmed Rossi would be out for 4–5 months.


title: Giuseppe Rossi

text: Rossi returned to the pitch on 30 August 2015, in a 3–1 away defeat to Torino; later that week he also agreed with his club to take a salary cut. On 1 October, he scored his first goal since coming back from his injury in Fiorentina's 4–0 away victory over Belenenses in the Europa League.


title: Giuseppe Rossi

text: On 22 January 2016, Rossi returned to La Liga by signing a loan deal until end of the season with Levante, in order to gain playing time, and a place in the Italian national side at Euro 2016. He made his club debut on 31 January, scoring in a 3–1 away defeat to Sevilla. On 13 March at the Estadi Ciutat de València, he scored the only goal of a win over city rivals Valencia CF, managed by his former United teammate Gary Neville. On 8 May, he scored a late winner in a 2–1 home win over title contenders Atlético Madrid, although the result was not sufficient to prevent the team from being relegated.


title: Giuseppe Rossi

text: On 29 August 2016, Rossi signed a one-year contract with Celta de Vigo, with an option for another year. He scored his first goal for the club on his debut, which came in a 1–1 away draw against Standard Liège in Celta's opening group match of the Europa League. He made his league debut with the club on 18 September, coming on as a substitute in a 0–0 away draw against Osasuna. On 3 April 2017, Rossi scored a hat-trick in a 3–1 home win over Las Palmas in La Liga; this was his first goal since he scored against Espanyol on 25 September 2016, and his first hat-trick since 20 October 2013, when he scored three goals for Fiorentina in a 4–2 home win against Juventus. On 9 April 2017, Rossi suffered the fifth serious injury of his career when he ruptured the ACL in his left knee in a game against SD Eibar, and was consequently ruled out of action for at least 6 months. Rossi became a free agent in July after Fiorentina allowed his contract to expire and he subsequently rejected an offer by Celta to remain with the Spanish side until January 2018.


title: Giuseppe Rossi

text: On 4 December 2017, Rossi was signed by Genoa on a free transfer. He made his debut for the club on 20 December, coming on as a second-half substitute in a 2–0 away defeat against Juventus in the round of 16 of the Coppa Italia.


title: Giuseppe Rossi

text: On 12 May 2018 Rossi failed a drug test following a Serie A match against Benevento, testing positive for the banned substance dorzolamide. Although the country's anti-doping prosecutor wanted Rossi to face a one-year ban for this offence, following a hearing with that took place on 1 October, Rossi was ultimately given a warning; afterward, Rossi's lawyer Sergio Puglisi claimed: "We don't understand how this substance ended up among Rossi's foods, there was no intentionality – the line of good faith and consistency prevailed." Rossi later tweeted: "A nightmare of four months is over. I only want to think about football."


title: Giuseppe Rossi

text: In January 2019, Rossi started training with his former club, Manchester United. In February of that year, Rossi was reported to have been invited to train with MLS side Los Angeles FC. On 14 October, his former club Villarreal announced that Rossi would start training with their first team. In an interview with Italian daily newspaper "Corriere della Sera" in December 2019, he stated that he was "ready to help out any Serie A team".


title: Giuseppe Rossi

text: Following a trial with the MLS club, Rossi was announced as a Real Salt Lake player on 27 February 2020. He made his club debut on 29 February, coming on as a late second–half substitute in a 0–0 away draw against Orlando City in the MLS. His contract option was declined by Salt Lake following their 2020 season.


title: Giuseppe Rossi

text: On 19 November 2021, after a few weeks of training with the club squad, Rossi was formally announced as a new signing for Italian Serie B club SPAL, on a deal until the end of the season.


title: Giuseppe Rossi

text: Rossi represented Italy at almost every youth level from under-16 to under-21 levels. In 2006, he was invited to a pre-World Cup training camp with the United States national team by coach Bruce Arena but declined, stating his desire to play for Italy. He was called up for the 2007 Under-21 European Championship by Italy under-21 head coach Pierluigi Casiraghi. The following year, he scored four goals at the 2008 Summer Olympics, making him the top scorer of the tournament, despite only reaching the quarter-finals with Italy, following a 3–2 loss to Belgium on 16 August, in which he scored twice from the penalty spot; his other two goals came in the opening match of the competition – a 3–0 win against Honduras on 7 August, in which he scored the second goal of the game from a penalty – and in Italy's second group match on 10 August – a 3–0 win over Korea Republic – in which he scored the opening goal.


title: Giuseppe Rossi

text: Italian national football team manager Marcello Lippi stated that had Rossi been fit, he would have received a call-up for the 2010 World Cup qualifiers in September 2008. Rossi was called up to the Italy squad in October 2008, making his senior debut for the national team as a second-half substitute in a 0–0 away draw against Bulgaria on 11 October, in a 2010 World Cup qualifier. Rossi scored his first goal for the Italian national team on 6 June 2009, in a friendly against Northern Ireland, at Pisa's Arena Garibaldi. He also scored two goals in a 3–1 win against his country of birth, the United States, in Italy's opening match of the 2009 FIFA Confederations Cup in South Africa on 15 June 2009, although Italy subsequently lost their next two matches and suffered a first-round elimination.


title: Giuseppe Rossi

text: Rossi was included in Lippi's provisional 28-man 2010 FIFA World Cup squad, which had been announced in May, but failed to make the cut for the final 23-man squad.


title: Giuseppe Rossi

text: On 17 November 2010, for his 18th cap for Italy, Rossi was picked by Italian manager Cesare Prandelli to wear the captain's armband for the first time ahead of the team's friendly against Romania.


title: Giuseppe Rossi

text: After a two-year absence from the national team due to injury, which saw him miss out on a place at Euro 2012, Rossi appeared in a 2014 World Cup qualifying match on 15 October 2013, as Italy drew 2–2 against Armenia at home. On 13 May 2014, Rossi was named in Italy's provisional 30-man squad for the 2014 FIFA World Cup, however on 1 June, it was announced that Rossi had not made the final 23-man World Cup squad.


title: Giuseppe Rossi

text: On 24 May 2016, Prandelli's successor as Italy's manager, Antonio Conte, released his 30-man shortlist for UEFA Euro 2016 roster; Rossi was not selected.


title: Giuseppe Rossi

text: A quick and mobile left-footed forward, Rossi is known for his overall attacking and creative style of play, as well as his work-rate, movement off the ball, his powerful and accurate striking ability, and instincts in the box. Regarded as one of the most promising Italian players of his generation in his youth, his playing style has often been compared to that of compatriot Alessandro Del Piero, due to his acceleration, strong technical skills, range of passing, dribbling talents, and his ability to either score goals or pick out a pass and create chances for teammates; he has also been compared to his namesake, 1982 World Cup-winning striker Paolo Rossi, due to his opportunism, pace, agility, and eye for goal. In 2013, former Fiorentina playmaker Giancarlo Antognoni likened Rossi to fellow former Fiorentina number ten Roberto Baggio, "In terms of his touch and creativity." Giuseppe Rossi is known for his ability to both finish off chances and link-up well with midfielders; due to his abilities, he often drops deep between the lines and is involved in the buildup of plays. Because of this, Rossi is able to play in a variety of attacking positions, including on the wings, as a supporting striker, as a lone-striker, and in an attacking midfield role. He is also an accurate penalty taker. Despite his talent, skill, and goalscoring ability, Rossi's playing time has been limited in recent seasons due to several recurring injury problems.


title: Giuseppe Rossi

text: In September 2021, he began his career as sports commentator for "Calcio e Cappuccino", an American television program dedicated to the Serie A and broadcast on CBS Sports Network and can be found via streaming on Paramount+.


title: Management of HIV/AIDS

text: The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same sex and opposite sex partners so long as the HIV-positive partner maintains an undetectable viral load.


title: Management of HIV/AIDS

text: Treatment has been so successful that in many parts of the world, HIV has become a chronic condition in which progression to AIDS is increasingly rare. Anthony Fauci, head of the United States National Institute of Allergy and Infectious Diseases, has written, "With collective and resolute action now and a steadfast commitment for years to come, an AIDS-free generation is indeed within reach." In the same paper, he noted that an estimated 700,000 lives were saved in 2010 alone by antiretroviral therapy. As another commentary in "The Lancet" noted, "Rather than dealing with acute and potentially life-threatening complications, clinicians are now confronted with managing a chronic disease that in the absence of a cure will persist for many decades."


title: Management of HIV/AIDS

text: The United States Department of Health and Human Services and the World Health Organization (WHO) recommend offering antiretroviral treatment to all patients with HIV. Because of the complexity of selecting and following a regimen, the potential for side effects, and the importance of taking medications regularly to prevent viral resistance, such organizations emphasize the importance of involving patients in therapy choices and recommend analyzing the risks and the potential benefits.


title: Management of HIV/AIDS

text: The WHO has defined health as more than the absence of disease. For this reason, many researchers have dedicated their work to better understanding the effects of HIV-related stigma, the barriers it creates for treatment interventions, and the ways in which those barriers can be circumvented.


title: Management of HIV/AIDS

text: There are six classes of drugs, which are usually used in combination, to treat HIV infection. Antiretroviral (ARV) drugs are broadly classified by the phase of the retrovirus life-cycle that the drug inhibits. Typical combinations include two nucleoside reverse-transcriptase inhibitors (NRTI) as a "backbone" along with one non-nucleoside reverse-transcriptase inhibitor (NNRTI), protease inhibitor (PI) or integrase inhibitors (also known as integrase nuclear strand transfer inhibitors or INSTIs) as a "base."


title: Management of HIV/AIDS

text: Entry inhibitors (or fusion inhibitors) interfere with binding, fusion and entry of HIV-1 to the host cell by blocking one of several targets. Maraviroc and enfuvirtide are the two available agents in this class. Maraviroc works by targeting CCR5, a co-receptor located on human helper T-cells. Caution should be used when administering this drug, however, due to a possible shift in tropism which allows HIV to target an alternative co-receptor such as CXCR4.


title: Management of HIV/AIDS

text: In rare cases, individuals may have a mutation in the CCR5 delta gene which results in a nonfunctional CCR5 co-receptor and in turn, a means of resistance or slow progression of the disease. However, as mentioned previously, this can be overcome if an HIV variant that targets CXCR4 becomes dominant. To prevent fusion of the virus with the host membrane, enfuvirtide can be used. Enfuvirtide is a peptide drug that must be injected and acts by interacting with the N-terminal heptad repeat of gp41 of HIV to form an inactive hetero six-helix bundle, therefore preventing infection of host cells.


title: Management of HIV/AIDS

text: Nucleoside reverse-transcriptase inhibitors (NRTI) and nucleotide reverse-transcriptase inhibitors (NtRTI) are nucleoside and nucleotide analogues which inhibit reverse transcription. HIV is an RNA virus, so it can not be integrated into the DNA in the nucleus of the human cell unless it is first "reverse" transcribed into DNA. Since the conversion of RNA to DNA is not naturally done in the mammalian cell, it is performed by a viral protein, reverse transcriptase, which makes it a selective target for inhibition. NRTIs are chain terminators. Once NRTIs are incorporated into the DNA chain, their lack of a 3' OH group prevents the subsequent incorporation of other nucleosides. Both NRTIs and NtRTIs act as competitive substrate inhibitors. Examples of NRTIs include zidovudine, abacavir, lamivudine, emtricitabine, and of NtRTIs – tenofovir and adefovir.


title: Management of HIV/AIDS

text: Non-nucleoside reverse-transcriptase inhibitors (NNRTI) inhibit reverse transcriptase by binding to an allosteric site of the enzyme; NNRTIs act as non-competitive inhibitors of reverse transcriptase. NNRTIs affect the handling of substrate (nucleotides) by reverse transcriptase by binding near the active site. NNRTIs can be further classified into 1st generation and 2nd generation NNRTIs. 1st generation NNRTIs include nevirapine and efavirenz. 2nd generation NNRTIs are etravirine and rilpivirine. HIV-2 is naturally resistant to NNRTIs.


title: Management of HIV/AIDS

text: Integrase inhibitors (also known as integrase nuclear strand transfer inhibitors or INSTIs) inhibit the viral enzyme integrase, which is responsible for integration of viral DNA into the DNA of the infected cell. There are several integrase inhibitors under clinical trial, and raltegravir became the first to receive FDA approval in October 2007. Raltegravir has two metal binding groups that compete for substrate with two Mg ions at the metal binding site of integrase. As of early 2022, four other clinically approved integrase inhibitors are elvitegravir, dolutegravir, bictegravir, and cabotegravir.


title: Management of HIV/AIDS

text: Protease inhibitors block the viral protease enzyme necessary to produce mature virions upon budding from the host membrane. Particularly, these drugs prevent the cleavage of gag and gag/pol precursor proteins. Virus particles produced in the presence of protease inhibitors are defective and mostly non-infectious. Examples of HIV protease inhibitors are lopinavir, indinavir, nelfinavir, amprenavir and ritonavir. Darunavir and atazanavir are recommended as first line therapy choices. Maturation inhibitors have a similar effect by binding to gag, but development of two experimental drugs in this class, bevirimat and vivecon, was halted in 2010. Resistance to some protease inhibitors is high. Second generation drugs have been developed that are effective against otherwise resistant HIV variants.


title: Management of HIV/AIDS

text: The life cycle of HIV can be as short as about 1.5 days from viral entry into a cell, through replication, assembly, and release of additional viruses, to infection of other cells. HIV lacks proofreading enzymes to correct errors made when it converts its RNA into DNA via reverse transcription. Its short life-cycle and high error rate cause the virus to mutate very rapidly, resulting in a high genetic variability. Most of the mutations either are inferior to the parent virus (often lacking the ability to reproduce at all) or convey no advantage, but some of them have a natural selection superiority to their parent and can enable them to slip past defenses such as the human immune system and antiretroviral drugs. The more active copies of the virus, the greater the possibility that one resistant to antiretroviral drugs will be made.


title: Management of HIV/AIDS

text: When antiretroviral drugs are used improperly, multi-drug resistant strains can become the dominant genotypes very rapidly. In the era before multiple drug classes were available (pre-1997), the reverse-transcriptase inhibitors zidovudine, didanosine, zalcitabine, stavudine, and lamivudine were used serially or in combination leading to the development of multi-drug resistant mutations.


title: Management of HIV/AIDS

text: In contrast, antiretroviral combination therapy defends against resistance by creating multiple obstacles to HIV replication. This keeps the number of viral copies low and reduces the possibility of a superior mutation. If a mutation that conveys resistance to one of the drugs arises, the other drugs continue to suppress reproduction of that mutation. With rare exceptions, no individual antiretroviral drug has been demonstrated to suppress an HIV infection for long; these agents must be taken in combinations in order to have a lasting effect. As a result, the standard of care is to use combinations of antiretroviral drugs. Combinations usually consist of three drugs from at least two different classes. This three drug combination is commonly known as a triple cocktail. Combinations of antiretrovirals are subject to positive and negative synergies, which limits the number of useful combinations.


title: Management of HIV/AIDS

text: Because of HIV's tendency to mutate, when patients who have started an antiretrovial regimen fail to take it regularly, resistance can develop. On the other hand, patients who take their medications regularly can stay on one regimen without developing resistance. This greatly increases life expectancy and leaves more drugs available to the individual should the need arise.


title: Management of HIV/AIDS

text: In recent years, drug companies have worked together to combine these complex regimens into single-pill fixed-dose combinations. More than 20 antiretroviral fixed-dose combinations have been developed. This greatly increases the ease with which they can be taken, which in turn increases the consistency with which medication is taken (adherence), and thus their effectiveness over the long-term.


title: Management of HIV/AIDS

text: Although antiretroviral therapy has helped to improve the quality of life of people living with HIV, there is still a need to explore other ways to further address the disease burden. One such potential strategy that was investigated was to add interleukin 2 as an adjunct to antiretroviral therapy for adults with HIV. A Cochrane review included 25 randomized controlled trials that were conducted across six countries. The researchers found that interleukin 2 increases the CD4 immune cells, but does not make a difference in terms of death and incidence of other infections. Furthermore, there is probably an increase in side-effects with interleukin 2. The findings of this review do not support the use of interleukin 2 as an add-on treatment to antiretroviral therapy for adults with HIV.


title: Management of HIV/AIDS

text: Antiretroviral drug treatment guidelines have changed over time. Before 1987, no antiretroviral drugs were available and treatment consisted of treating complications from opportunistic infections and malignancies. After antiretroviral medications were introduced, most clinicians agreed that HIV positive patients with low CD4 counts should be treated, but no consensus formed as to whether to treat patients with high CD4 counts.


title: Management of HIV/AIDS

text: In April 1995, Merck and the National Institute of Allergy and Infectious Diseases began recruiting patients for a trial examining the effects of a three drug combination of the protease inhibitor indinavir and two nucleoside analogs. illustrating the substantial benefit of combining 2 NRTIs with a new class of antiretrovirals, protease inhibitors, namely indinavir. Later that year David Ho became an advocate of this "hit hard, hit early" approach with aggressive treatment with multiple antiretrovirals early in the course of the infection. Later reviews in the late 90s and early 2000s noted that this approach of "hit hard, hit early" ran significant risks of increasing side effects and development of multidrug resistance, and this approach was largely abandoned. The only consensus was on treating patients with advanced immunosuppression (CD4 counts less than 350/μL). Treatment with antiretrovirals was expensive at the time, ranging from $10,000 to $15,000 a year.


title: Management of HIV/AIDS

text: The timing of when to start therapy has continued to be a core controversy within the medical community, though recent studies have led to more clarity. The NA-ACCORD study observed patients who started antiretroviral therapy either at a CD4 count of less than 500 versus less than 350 and showed that patients who started ART at lower CD4 counts had a 69% increase in the risk of death. In 2015 the START and TEMPRANO studies both showed that patients lived longer if they started antiretrovirals at the time of their diagnosis, rather than waiting for their CD4 counts to drop to a specified level.


title: Management of HIV/AIDS

text: Other arguments for starting therapy earlier are that people who start therapy later have been shown to have less recovery of their immune systems, and higher CD4 counts are associated with less cancer.


title: Management of HIV/AIDS

text: The European Medicines Agency (EMA) has recommended the granting of marketing authorizations for two new antiretroviral (ARV) medicines, rilpivirine (Rekambys) and cabotegravir (Vocabria), to be used together for the treatment of people with human immunodeficiency virus type 1 (HIV-1) infection. The two medicines are the first ARVs that come in a long-acting injectable formulation. This means that instead of daily pills, people receive intramuscular injections monthly or every two months.


title: Management of HIV/AIDS

text: The combination of Rekambys and Vocabria injection is intended for maintenance treatment of adults who have undetectable HIV levels in the blood (viral load less than 50 copies/ml) with their current ARV treatment, and when the virus has not developed resistance to certain class of anti-HIV medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (INIs).


title: Management of HIV/AIDS

text: A separate argument for starting antiretroviral therapy that has gained more prominence is its effect on HIV transmission. ART reduces the amount of virus in the blood and genital secretions. This has been shown to lead to dramatically reduced transmission of HIV when one partner with a suppressed viral load (<50 copies/ml) has sex with a partner who is HIV negative. In clinical trial HPTN 052, 1763 serodiscordant heterosexual couples in 9 countries were planned to be followed for at least 10 years, with both groups receiving education on preventing HIV transmission and condoms, but only one group getting ART. The study was stopped early (after 1.7 years) for ethical reasons when it became clear that antiviral treatment provided significant protection. Of the 28 couples where cross-infection had occurred, all but one had taken place in the control group consistent with a 96% reduction in risk of transmission while on ART. The single transmission in the experimental group occurred early after starting ART before viral load was likely to be suppressed. Pre-exposure prophylaxis (PrEP) provides HIV-negative individuals with medication—in conjunction with safer-sex education and regular HIV/STI screenings—in order to reduce the risk of acquiring HIV. In 2011, the journal "Science" gave the Breakthrough of the Year award to treatment as prevention.


title: Management of HIV/AIDS

text: In July 2016 a consensus document was created by the Prevention Access Campaign which has been endorsed by over 400 organisations in 58 countries. The consensus document states that the risk of HIV transmission from a person living with HIV who has been undetectable for a minimum of six months is negligible to non-existent, with negligible being defined as "so small or unimportant to be not worth considering". The Chair of the British HIV Association (BHIVA), Chloe Orkin, stated in July 2017 that 'there should be no doubt about the clear and simple message that a person with sustained, undetectable levels of HIV virus in their blood cannot transmit HIV to their sexual partners.'


title: Management of HIV/AIDS

text: Furthermore, the PARTNER study, which ran from 2010 to 2014, enrolled 1166 serodiscordant couples (where one partner is HIV positive and the other is negative) in a study that found that the estimated rate of transmission through any condomless sex with the HIV-positive partner taking ART with an HIV load less than 200 copies/ml was zero.


title: Management of HIV/AIDS

text: In summary, as the WHO HIV treatment guidelines state, "The ARV regimens now available, even in the poorest countries, are safer, simpler, more effective and more affordable than ever before."


title: Management of HIV/AIDS

text: There is a consensus among experts that, once initiated, antiretroviral therapy should never be stopped. This is because the selection pressure of incomplete suppression of viral replication in the presence of drug therapy causes the more drug sensitive strains to be selectively inhibited. This allows the drug resistant strains to become dominant. This in turn makes it harder to treat the infected individual as well as anyone else they infect. One trial showed higher rates of opportunistic infections, cancers, heart attacks and death in patients who periodically interrupted their ART.


title: Management of HIV/AIDS

text: There are several treatment guidelines for HIV-1 infected adults in the developed world (that is, those countries with access to all or most therapies and laboratory tests). In the United States there are both the International AIDS Society-USA (IAS-USA) (a 501(c)(3) not-for-profit organization in the US) as well as the US government's Department of Health and Human Services guidelines. In Europe there are the European AIDS Clinical Society guidelines.


title: Management of HIV/AIDS

text: For resource limited countries, most national guidelines closely follow the World Health Organization (WHO) guidelines.


title: Management of HIV/AIDS

text: The guidelines use new criteria to consider starting HAART, as described below. However, there remain a range of views on this subject and the decision of whether to commence treatment ultimately rests with the patient and his or her doctor.


title: Management of HIV/AIDS

text: Baseline resistance is the presence of resistance mutations in patients who have never been treated before for HIV. In countries with a high rate of baseline resistance, resistance testing is recommended before starting treatment; or, if the initiation of treatment is urgent, then a "best guess" treatment regimen should be started, which is then modified on the basis of resistance testing. In the UK, there is 11.8% medium to high-level resistance at baseline to the combination of efavirenz + zidovudine + lamivudine, and 6.4% medium to high level resistance to stavudine + lamivudine + nevirapine. In the US, 10.8% of one cohort of patients who had never been on ART before had at least one resistance mutation in 2005. Various surveys in different parts of the world have shown increasing or stable rates of baseline resistance as the era of effective HIV therapy continues. With baseline resistance testing, a combination of antiretrovirals that are likely to be effective can be customized for each patient.


title: Management of HIV/AIDS

text: Most HAART regimens consist of three drugs: 2 NRTIs ("backbone")+ a PI/NNRTI/INSTI ("base"). Initial regimens use "first-line" drugs with a high efficacy and low side-effect profile.


title: Management of HIV/AIDS

text: The US DHHS preferred initial regimens for adults and adolescents in the United States, as of April 2015, are:


title: Management of HIV/AIDS

text: In the case of the protease inhibitor based regimens, ritonavir is used at low doses to inhibit cytochrome p450 enzymes and "boost" the levels of other protease inhibitors, rather than for its direct antiviral effect. This boosting effect allows them to be taken less frequently throughout the day. Cobicistat is used with elvitegravir for a similar effect but does not have any direct antiviral effect itself.


title: Management of HIV/AIDS

text: In the first six months after infection HIV viral loads tend to be elevated and people are more often symptomatic than in later latent phases of HIV disease. There may be special benefits to starting antiretroviral therapy early during this acute phase, including lowering the viral "set-point" or baseline viral load, reduce the mutation rate of the virus, and reduce the size of the viral reservoir (See section below on viral reservoirs). The SPARTAC trial compared 48 weeks of ART vs 12 weeks vs no treatment in acute HIV infection and found that 48 weeks of treatment delayed the time to decline in CD4 count below 350 cells per ml by 65 weeks and kept viral loads significantly lower even after treatment was stopped.


title: Management of HIV/AIDS

text: Since viral loads are usually very high during acute infection, this period carries an estimated 26 times higher risk of transmission. By treating acutely infected patients, it is presumed that it could have a significant impact on decreasing overall HIV transmission rates since lower viral loads are associated with lower risk of transmission (See section on treatment as prevention). However an overall benefit has not been proven and has to be balanced with the risks of HIV treatment. Therapy during acute infection carries a grade BII recommendation from the US DHHS.


title: Management of HIV/AIDS

text: HIV can be especially harmful to infants and children, with one study in Africa showing that 52% of untreated children born with HIV had died by age 2. By five years old, the risk of disease and death from HIV starts to approach that of young adults. The WHO recommends treating all children less than 5 years old, and starting all children older than 5 with stage 3 or 4 disease or CD4 <500 cells/ml. DHHS guidelines are more complicated but recommend starting all children less than 12 months old and children of any age who have symptoms.


title: Management of HIV/AIDS

text: As for which antiretrovirals to use, this is complicated by the fact that many children who are born to mothers with HIV are given a single dose of nevirapine (an NNRTI) at the time of birth to prevent transmission. If this fails it can lead to NNRTI resistance. Also, a large study in Africa and India found that a PI based regimen was superior to an NNRTI based regimen in children less than 3 years who had never been exposed to NNRTIs in the past. Thus the WHO recommends PI based regimens for children less than 3.


title: Management of HIV/AIDS

text: A systematic review assessed the effects and safety of abacavir-containing regimens as first-line therapy for children between 1 month and 18 years of age when compared to regimens with other NRTIs. This review included two trials and two observational studies with almost eleven thousand HIV infected children and adolescents. They measured virologic suppression, death and adverse events. The authors found that there is no meaningful difference between abacavir-containing regimens and other NRTI-containing regimens. The evidence is of low to moderate quality and therefore it is likely that future research may change these findings.


title: Management of HIV/AIDS

text: The goals of treatment for pregnant women include the same benefits to the mother as in other infected adults as well as prevention of transmission to her child. The risk of transmission from mother to child is proportional to the plasma viral load of the mother. Untreated mothers with a viral load >100,000 copies/ml have a transmission risk of over 50%. The risk when viral loads are < 1000 copies/ml are less than 1%. ART for mothers both before and during delivery and to mothers and infants after delivery are recommended to substantially reduce the risk of transmission. The mode of delivery is also important, with a planned Caesarian section having a lower risk than vaginal delivery or emergency Caesarian section.


title: Management of HIV/AIDS

text: HIV can also be detected in breast milk of infected mothers and transmitted through breast feeding. The WHO balances the low risk of transmission through breast feeding from women who are on ART with the benefits of breastfeeding against diarrhea, pneumonia and malnutrition. It also strongly recommends that breastfeeding infants receive prophylactic ART. In the US, the DHHS recommends against women with HIV breastfeeding.


title: Management of HIV/AIDS

text: With improvements in HIV therapy, several studies now estimate that patients on treatment in high-income countries can expect a normal life expectancy. This means that a higher proportion of people living with HIV are now older and research is ongoing into the unique aspects of HIV infection in the older adult. There is data that older people with HIV have a blunted CD4 response to therapy but are more likely to achieve undetectable viral levels. However, not all studies have seen a difference in response to therapy. The guidelines do not have separate treatment recommendations for older adults, but it is important to take into account that older patients are more likely to be on multiple non-HIV medications and consider drug interactions with any potential HIV medications. There are also increased rates of HIV associated non-AIDS conditions (HANA) such as heart disease, liver disease and dementia that are multifactorial complications from HIV, associated behaviors, coinfections like hepatitis B, hepatitis C, and human papilloma virus (HPV) as well as HIV treatment.


title: Management of HIV/AIDS

text: Many factors may contribute to depression in adults living with HIV, such as the effects of the virus on the brain, other infections or tumours, antiretroviral drugs and other medical treatment. Rates of major depression are higher in people living with HIV compared to the general population, and this may negatively influence antiretroviral treatment. In a systematic review, Cochrane researchers assessed whether giving antidepressants to adults living with both HIV and depression may improve depression. Ten trials, of which eight were done in high-income countries, with 709 participants were included. Results indicated that antidepressants may be better in improving depression compared to placebo, but the quality of the evidence is low and future research is likely to impact on the findings.


title: Management of HIV/AIDS

text: Suppressing the viral load to undetectable levels (<50 copies per ml) is the primary goal of ART. This should happen by 24 weeks after starting combination therapy. Viral load monitoring is the most important predictor of response to treatment with ART. Lack of viral load suppression on ART is termed virologic failure. Levels higher than 200 copies per ml is considered virologic failure, and should prompt further testing for potential viral resistance.


title: Management of HIV/AIDS

text: Research has shown that people with an undetectable viral load are unable to transmit the virus through condomless sex with a partner of either gender. The 'Swiss Statement' of 2008 described the chance of transmission as 'very low' or 'negligible,' but multiple studies have since shown that this mode of sexual transmission is impossible where the HIV-positive person has a consistently undetectable viral load. This discovery has led to the formation of the Prevention Access Campaign are their 'U=U' or 'Undetectable=Untransmittable' public information strategy, an approach that has gained widespread support amongst HIV/AIDS-related medical, charitable, and research organisations. The studies demonstrating that U=U is an effective strategy for preventing HIV transmission in serodiscordant couples so long as "the partner living with HIV [has] a durably suppressed viral load" include: Opposites Attract, PARTNER 1, PARTNER 2, (for male-male couples) and HPTN052 (for heterosexual couples). In these studies, couples where one partner was HIV-positive and one partner was HIV-negative were enrolled and regular HIV testing completed. In total from the four studies, 4097 couples were enrolled over four continents and 151,880 acts of condomless sex were reported, there were zero phylogenetically linked transmissions of HIV where the positive partner had an undetectable viral load. Following this the U=U consensus statement advocating the use of 'zero risk' was signed by hundreds of individuals and organisations including the US CDC, British HIV Association and "The Lancet" medical journal. The importance of the final results of the PARTNER 2 study were described by the medical director of the Terrence Higgins Trust as "impossible to overstate," while lead author Alison Rodger declared that the message that "undetectable viral load makes HIV untransmittable ... can help end the HIV pandemic by preventing HIV transmission." The authors summarised their findings in "The Lancet" as follows:


title: Management of HIV/AIDS

text: This result is consistent with the conclusion presented by Anthony S. Fauci, the Director of the National Institute of Allergy and Infectious Diseases for the U.S. National Institutes of Health, and his team in a viewpoint published in the "Journal of the American Medical Association", that U=U is an effective HIV prevention method when an undetectable viral load is maintained.


title: Management of HIV/AIDS

text: CD4 cell counts are another key measure of immune status and ART effectiveness. CD4 counts should rise 50 to 100 cells per ml in the first year of therapy. There can be substantial fluctuation in CD4 counts of up to 25% based on the time of day or concomitant infections. In one long-term study, the majority of increase in CD4 cell counts was in the first two years after starting ART with little increase afterwards. This study also found that patients who began ART at lower CD4 counts continued to have lower CD4 counts than those who started at higher CD4 counts. When viral suppression on ART is achieved but without a corresponding increase in CD4 counts it can be termed immunologic nonresponse or immunologic failure. While this is predictive of worse outcomes, there is no consensus on how to adjust therapy to immunologic failure and whether switching therapy is beneficial. DHHS guidelines do not recommend switching an otherwise suppressive regimen.


title: Management of HIV/AIDS

text: Innate lymphoid cells (ILC) are another class of immune cell that is depleted during HIV infection. However, if ART is initiated before this depletion at around 7 days post infection, ILC levels can be maintained. While CD4 cell counts typically replenish after effective ART, ILCs depletion is irreversible with ART initiated after the depletion despite suppression of viremia. Since one of the roles of ILCs is to regulate the immune response to commensal bacteria and to maintain an effective gut barrier, it has been hypothesized that the irreversible depletion of ILCs plays a role in the weakened gut barrier of HIV patients, even after successful ART.


title: Management of HIV/AIDS

text: In patients who have persistently detectable viral loads while taking ART, tests can be done to investigate whether there is drug resistance. Most commonly a genotype is sequenced which can be compared with databases of other HIV viral genotypes and resistance profiles to predict response to therapy. Resistance testing may improve virological outcomes in those who have treatment failures. However, there is lack of evidence of effectiveness of such testing in those who have not done any treatment before.


title: Management of HIV/AIDS

text: If there is extensive resistance a phenotypic test of a patient's virus against a range of drug concentrations can be performed, but is expensive and can take several weeks, so genotypes are generally preferred. Using information from a genotype or phenotype, a regimen of 3 drugs from at least 2 classes is constructed that will have the highest probability of suppressing the virus. If a regimen cannot be constructed from recommended first line agents it is termed salvage therapy, and when 6 or more drugs are needed it is termed mega-HAART.


title: Management of HIV/AIDS

text: Drug holidays (or "structured treatment interruptions") are intentional discontinuations of antiretroviral drug treatment. As mentioned above, randomized controlled studies of structured treatment interruptions have shown higher rates of opportunistic infections, cancers, heart attacks and death in patients who took drug holidays. With the exception of post-exposure prophylaxis (PEP), treatment guidelines do not call for the interruption of drug therapy once it has been initiated.


title: Management of HIV/AIDS

text: The NRTIs can interfere with mitochondrial DNA synthesis and lead to high levels of lactate and lactic acidosis, liver steatosis, peripheral neuropathy, myopathy and lipoatrophy. First-line NRTIs such as lamivudine/emtrictabine, tenofovir, and abacavir are less likely to cause mitochondrial dysfunction.


title: Management of HIV/AIDS

text: Mitochondrial Haplogroups(mtDNA), non pathologic mutations inherited from the maternal line, have been linked to the efficacy of CD4+ count following ART. Idiosyncratic toxicity with mtDNA haplogroup is also well studied.(Boeisteril et al., 2007).


title: Management of HIV/AIDS

text: NNRTIs are generally safe and well tolerated. The main reason for discontinuation of efavirenz is neuro-psychiatric effects including suicidal ideation. Nevirapine can cause severe hepatotoxicity, especially in women with high CD4 counts.


title: Management of HIV/AIDS

text: Protease inhibitors (PIs) are often given with ritonavir, a strong inhibitor of cytochrome P450 enzymes, leading to numerous drug-drug interactions. They are also associated with lipodystrophy, elevated triglycerides and elevated risk of heart attack.


title: Management of HIV/AIDS

text: Integrase inhibitors (INSTIs) are among the best tolerated of the antiretrovirals with excellent short and medium term outcomes. Given their relatively new development there is less long term safety data. They are associated with an increase in creatinine kinase levels and rarely myopathy.


title: Management of HIV/AIDS

text: When people are exposed to HIV-positive infectious bodily fluids either through skin puncture, contact with mucous membranes or contact with damaged skin, they are at risk for acquiring HIV. Pooled estimates give a risk of transmission with puncture exposures of 0.3% and mucous membrane exposures 0.63%. United States guidelines state that "feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody." Given the rare nature of these events, rigorous study of the protective abilities of antiretrovirals are limited but do suggest that taking antiretrovirals afterwards can prevent transmission. It is unknown if three medications are better than two. The sooner after exposure that ART is started the better, but after what period they become ineffective is unknown, with the US Public Health Service Guidelines recommending starting prophylaxis up to a week after exposure. They also recommend treating for a duration of four weeks based on animal studies. Their recommended regimen is emtricitabine + tenofovir + raltegravir (an INSTI). The rationale for this regimen is that it is "tolerable, potent, and conveniently administered, and it has been associated with minimal drug interactions." People who are exposed to HIV should have follow up HIV testing at six, 12, and 24 weeks.


title: Management of HIV/AIDS

text: Women with HIV have been shown to have decreased fertility which can affect available reproductive options. In cases where the woman is HIV negative and the man is HIV positive, the primary assisted reproductive method used to prevent HIV transmission is sperm washing followed by intrauterine insemination (IUI) or in vitro fertilization (IVF). Preferably this is done after the man has achieved an undetectable plasma viral load. In the past there have been cases of HIV transmission to an HIV-negative partner through processed artificial insemination, but a large modern series in which followed 741 couples where the man had a stable viral load and semen samples were tested for HIV-1, there were no cases of HIV transmission.


title: Management of HIV/AIDS

text: For cases where the woman is HIV positive and the man is HIV negative, the usual method is artificial insemination. With appropriate treatment the risk of mother-to-child infection can be reduced to below 1%.


title: Management of HIV/AIDS

text: Several buyers clubs sprang up since 1986 to combat HIV. The drug zidovudine (AZT), a nucleoside reverse-transcriptase inhibitor (NRTI), was not effective on its own. It was approved by the US FDA in 1987. The FDA bypassed stages of its review for safety and effectiveness in order to distribute this drug earlier. Subsequently, several more NRTIs were developed but even in combination were unable to suppress the virus for long periods of time and patients still inevitably died. To distinguish from this early antiretroviral therapy (ART), the term highly active antiretroviral therapy (HAART) was introduced. In 1996 two sequential publications in "The New England Journal of Medicine" by Hammer and colleagues and Gulick and colleagues illustrated the substantial benefit of combining 2 NRTIs with a new class of antiretrovirals, protease inhibitors, namely indinavir. This concept of 3-drug therapy was quickly incorporated into clinical practice and rapidly showed impressive benefit with a 60% to 80% decline in rates of AIDS, death, and hospitalization.


title: Management of HIV/AIDS

text: As HAART became widespread, fixed dose combinations were made available to ease the administration. Later, the term combination antiretroviral therapy (cART) gained favor with some physicians as a more accurate name, not conveying to patients any misguided idea of the nature of the therapy. Today multidrug, highly effective regimens are long since the default in ART, which is why they are increasingly called simply ART instead of HAART or cART. This retronymic process is linguistically comparable to the way that the words "electronic computer" and "digital computer" at first were needed to make useful distinctions in computing technology, but with the later irrelevance of the distinction, "computer" alone now covers their meaning. Thus as "all computers are digital now", so "all ART is combination ART now." However, the names HAART and cART, reinforced by thousands of earlier mentions in medical literature still being regularly cited, also remain in use.


title: Management of HIV/AIDS

text: People living with HIV can expect to live a nearly normal life span if able to achieve durable viral suppression on combination antiretroviral therapy. However this requires lifelong medication and will still have higher rates of cardiovascular, kidney, liver and neurologic disease. This has prompted further research towards a cure for HIV.


title: Management of HIV/AIDS

text: The so-called "Berlin patient" has been potentially cured of HIV infection and has been off of treatment since 2006 with no detectable virus. This was achieved through two bone marrow transplants that replaced his immune system with a donor's that did not have the CCR5 cell surface receptor, which is needed for some variants of HIV to enter a cell. Bone marrow transplants carry their own significant risks including potential death and was only attempted because it was necessary to treat a blood cancer he had. Attempts to replicate this have not been successful and given the risks, expense and rarity of CCR5 negative donors, bone marrow transplant is not seen as a mainstream option. It has inspired research into other methods to try to block CCR5 expression through gene therapy. A procedure zinc-finger nuclease-based gene knockout has been used in a Phase I trial of 12 humans and led to an increase in CD4 count and decrease in their viral load while off antiretroviral treatment. Attempt to reproduce this failed in 2016. Analysis of the failure showed that gene therapy only successfully treats 11-28% of cells, leaving the majority of CD4+ cells capable of being infected. The analysis found that only patients where less than 40% of cells were infected had reduced viral load. The Gene therapy was not effective if the native CD4+ cells remained. This is the main limitation which must be overcome for this treatment to become effective.


title: Management of HIV/AIDS

text: After the "Berlin patient", two additional patients with both HIV infection and cancer were reported to have no traceable HIV virus after successful stem cell transplants. Virologist Annemarie Wensing of the University Medical Center Utrecht announced this development during her presentation at the 2016 "Towards an HIV Cure" symposium. However, these two patients are still on antiretroviral therapy, which is not the case for the Berlin patient. Therefore, it is not known whether or not the two patients are cured of HIV infection. The cure might be confirmed if the therapy were to be stopped and no viral rebound occurred.


title: Management of HIV/AIDS

text: In March 2019, a second patient, referred to as the "London Patient", was confirmed to be in complete remission of HIV. Like the Berlin Patient, the London Patient received a bone marrow transplant from a donor who has the same CCR5 mutation. He has been off antiviral drugs since September 2017, indicating the Berlin Patient was not a "one-off".


title: Management of HIV/AIDS

text: Alternative approaches aiming to mimic one’s biological immunity to HIV through the absence or mutation of the CCR5 gene is being conducted in current research efforts. The efforts of which are done through the introduction of induced pluripotent stem cells that have been CCR5 disrupted through the CRISPR/Cas9 gene editing system.


title: Management of HIV/AIDS

text: The main obstacle to complete elimination of HIV infection by conventional antiretroviral therapy is that HIV is able to integrate itself into the DNA of host cells and rest in a latent state, while antiretrovirals only attack actively replicating HIV. The cells in which HIV lies dormant are called the viral reservoir, and one of the main sources is thought to be central memory and transitional memory CD4+ T cells. In 2014 there were reports of the cure of HIV in two infants, presumably due to the fact that treatment was initiated within hours of infection, preventing HIV from establishing a deep reservoir. There is work being done to try to activate reservoir cells into replication so that the virus is forced out of latency and can be attacked by antiretrovirals and the host immune system. Targets include histone deacetylase (HDAC) which represses transcription and if inhibited can lead to increased cell activation. The HDAC inhibitors valproic acid and vorinostat have been used in human trials with only preliminary results so far.


title: Management of HIV/AIDS

text: Even with all latent virus deactivated, it is thought that a vigorous immune response will need to be induced to clear all the remaining infected cells. Strategies include using cytokines to restore CD4+ cell counts as well as therapeutic vaccines to prime immune responses. One such candidate vaccine is Tat Oyi, developed by Biosantech. This vaccine is based on the HIV protein tat. Animal models have shown the generation of neutralizing antibodies and lower levels of HIV viremia.


title: Management of HIV/AIDS

text: HIV vaccine development is an active area of research and an important tool for managing the global AIDS epidemic. Research into a vaccine for HIV has been ongoing for decades with no lasting success for preventing infection. The rapid development, though, of mRNA vaccines to deal with the COVID-19 pandemic may provide a new path forward.


title: Management of HIV/AIDS

text: Like SARS-CoV-2, the virus that causes COVID-19, HIV has a spike protein. In retroviruses like HIV, the spike protein is formed by two proteins expressed by the Env gene. This viral envelope binds to the host cell’s receptor and is what gains the virus entry into the cell. With mRNA vaccines, mRNA or messenger RNA, contains the instructions for how to make the spike protein. The mRNA is put into lipid-based nanoparticles for drug delivery. This was a key breakthrough in optimizing the efficiency and efficacy of in vivo delivery. When the vaccine is injected, the mRNA enters cells and joins up with a ribosome. The ribosome then translates the mRNA instructions into the spike protein. The immune system detects the presence of the spike protein and B cells, a type of white blood cell, begin to develop antibodies. Should the actual virus later enter the system, the external spike protein will be recognized by memory B cells, whose function is to memorize the characteristics of the original antigen. Memory B cells then produce the antibodies, hopefully destroying the virus before it can bind to another cell and repeat the HIV life cycle.


title: Management of HIV/AIDS

text: SARS-CoV-2 and HIV-1 have similarities—notably both are RNA viruses—but there are important differences. As a retrovirus, HIV-1 can insert a copy of its RNA genome into the host’s DNA, making total eradication more difficult. The virus is also highly mutable making it a challenge for the adaptive immune system to develop a response. As a chronic infection, HIV-1 and the adaptive immune system undergo reciprocal selective pressures leading to the evolutionary arms race of coevolution.


title: Management of HIV/AIDS

text: Broadly neutralizing HIV-1 antibodies, or bnAbs, have been shown to attach to the Env spike protein envelope regardless of the specific HIV mutations. This bodes well for vaccine development. Complicating matters, though, naive B cells—mature B cells not yet exposed to any antigen and are the progenitors of bnAbs—are rare. Further, the mutation events needed to turn these B cells into bnAbs are also rare. Because of this, there is a growing consensus that an effective HIV vaccine will need to create not only humoral (antibody-mediated) immunity, but a T-cell-mediated immunity.


title: Management of HIV/AIDS

text: mRNA vaccines have advantages over traditional vaccines which may help deal with some of the challenges presented by the HIV virus. The mRNA in the vaccine only codes for the protein spike, not the whole virus, so the possibility of reverse transcription, where the virus copies its genetic material into the host’s genome, is not present. Another advantage when compared to traditional vaccines is the speed of development. mRNA vaccines take months not years, which means a multipart sequential vaccine regime is possible.


title: Management of HIV/AIDS

text: Attempts to elicit an immune response that triggers broadly neutralizing antibodies (bnAbs) with a single vaccine dose have been unsuccessful. A multipart sequential mRNA vaccine regime, however, might guide the immune response in the right direction. The first shot triggers an immune response for the correct naive B cells. Later vaccinations encourage the development of these cells further, eventually turning them into memory b cells, and later into plasma cells, which can secrete the broadly neutralizing antibodies:In essence, the sequential immunization approach represents an attempt to mimic Env evolution that would occur with natural infection…. In contrast to traditional prime/boost strategies, in which the same immunogen is used repeatedly for vaccination, the sequential immunization approach relies on a series of different immunogens with the goal of eventually inducing bnAb(s).A Phase 1 clinical trial by Scripps Research and the International AIDS Vaccine Initiative of an mRNA vaccine showed that 97 percent of participants had the desired initial “priming” immune response of naive b cells. This is a positive result for developing the first shot in a vaccine sequence. Moderna is partnering with Scripps and the International AIDS Vaccine Initiative for a follow-up phase 1 clinical trial of an HIV mRNA vaccine (mRNA-1644) starting later in 2021.


title: Management of HIV/AIDS

text: Direct-to-consumer and other advertisements for HIV drugs in the past were criticized for their use of healthy, glamorous models rather than typical people with HIV/AIDS. Usually, these people will present with debilitating conditions or illnesses as a result of HIV/AIDS. In contrast, by featuring people in unrealistically strenuous activities, such as mountain climbing; this proved to be offensive and insensitive to the suffering of people who are HIV positive. The US FDA reprimanded multiple pharmaceutical manufacturers for publishing such adverts in 2001, as the misleading advertisements harmed consumers by implying unproven benefits and failing to disclose important information about the drugs.


title: Management of HIV/AIDS

text: Overall, some drug companies chose not to present their drugs in a realistic way, which consequently harmed the general public's ideas, suggesting that HIV would not affect you as much as suggested. This led to people not wanting to get tested, for fear of being HIV positive, because at the time (in the 80s and 90s particularly), having contracted HIV was seen as a death sentence, as there was no known cure.


title: Management of HIV/AIDS

text: The preamble to the World Health Organization's Constitution defines health as "a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity." Those living with HIV today are met with other challenges that go beyond the singular goal of lowering their viral load. A 2009 meta-analysis studying the correlates of HIV-stigma found that individuals living with higher stigma burden were more likely to have poorer physical and mental health. Insufficient social support and delayed diagnosis due to decreased frequency of HIV testing and knowledge of risk reduction were cited as some of the reasons. People living with HIV (PLHIV) have lower health related quality of life (HRQoL) scores than do the general population. The stigma of having HIV is often compounded with the stigma of identifying with the LGBTQ community or the stigma of being an injecting drug user (IDU) even though heterosexual sexual transmission accounts for 85% of all HIV-1 infections worldwide. AIDS has been cited as the most heavily stigmatized medical condition among infectious diseases. Part of the consequence of this stigma toward PLHIV is the belief that they are seen as responsible for their status and less deserving of treatment.


title: Management of HIV/AIDS

text: A 2016 study sharing the WHO's definition of health critiques its 90-90-90 target goal, which is part of a larger strategy that aims to eliminate the AIDS epidemic as a public health threat by 2030, by arguing that it does not go far enough in ensuring the holistic health of PLHIV. The study suggests that maintenance of HIV and AIDS should go beyond the suppression of viral load and the prevention of opportunistic infection. It proposes adding a 'fourth 90' addressing a new 'quality of life' target that would focus specifically on increasing the quality of life for those that are able to suppress their viral load to undetectable levels along with new metrics to track the progress toward that target. This study serves as an example of the shifting paradigm in the dynamics of the health care system from being heavily 'disease-oriented' to more 'human-centered'. Though questions remain of what exactly a more 'human-centered' method of treatment looks like in practice, it generally aims to ask what kind of support, other than medical support, PLHIV need to cope with and eliminate HIV-related stigmas. Campaigns and marketing aimed at educating the general public in order to reduce any misplaced fears of HIV contraction is one example. Also encouraged is the capacity-building and guided development of PLHIV into more leadership roles with the goal of having a greater representation of this population in decision making positions. Structural legal intervention has also been proposed, specifically referring to legal interventions to put in place protections against discrimination and improve access to employment opportunities. On the side of the practitioner, greater competence for the experience of people living with HIV is encouraged alongside the promotion of an environment of nonjudgment and confidentiality.


title: Management of HIV/AIDS

text: Psychosocial group interventions such as psychotherapy, relaxation, group support, and education may have some beneficial effects on depression in HIV positive people.


title: Management of HIV/AIDS

text: The successful treatment and management of HIV/AIDS is affected by a plethora of factors which ranges from successfully taking prescribed medications, preventing opportunistic infection, and food access etc. Food insecurity is a condition in which households lack access to adequate food because of limited money or other resources. Food insecurity is a global issue that have affect billions of people yearly including those living in developed countries.


title: Management of HIV/AIDS

text: Food insecurity is a major public health disparity in the United States of America, which significantly affects minority groups, people living at or below the poverty line, and those who are living with one or more morbidity. As of December 31, 2017, there were approximately 126,742 people living with HIV/AIDS (PLWHA) in NYC, of whom 87.6% can be described as living with some level of poverty and food insecurity as reported by the NYC Department of Health March 31, 2019. Having access to a consistent food supply that is safe and healthy is an important part in the treatment and management of HIV/AIDS. PLWHA are also greatly affected by food inequities and food deserts which causes them to be food insecure. Food insecurity, which can cause malnutrition, can also negatively impact HIV treatment and recovery from opportunistic infections. Similarly, PLWHA require additional calories and nutritionally support that require foods free from contamination to prevent further immunocompromising. Food insecurity can further exacerbate the progression of HIV/AIDS and can prevent PLWHA from consistently following their prescribed regimen, which will lead to poor outcomes.


title: Management of HIV/AIDS

text: It is imperative that these food insecurity among PLWHA are addressed and rectified to reduce this health inequity. It is important to recognized that socioeconomic status, access to medical care, geographic location, public policy, race and ethnicity all play a pivotal role in the treatment and management of HIV/AIDS. The lack of sufficient and constant income does limit the options for food, treatment, and medications. The same can be inferred for those who are among the oppressed groups in society who are marginalized and may be less inclined or encouraged to seek care and assistance. Endeavors to address food insecurity should be included in HIV treatment programs and may help improve health outcomes if it also focuses on health equity among the diagnosed as much as it focuses on medications. Access to consistently safe and nutritious foods is one of the most important facets in ensuring PLWHA are being provided the best possible care. By altering the narratives for HIV treatment so that more support can be garnered to reduce food insecurity and other health disparities mortality rates will decrease for people living with HIV/AIDS.


title: Lada Samara

text: The VAZ-2108, known as the Lada Samara in much of Western Europe (codenamed and later officially badged as the Lada Sputnik in its native Russia), is a series of small family cars produced by Soviet/Russian vehicle manufacturer AvtoVAZ under the Lada brand between 1984 and 2013. The model name Samara originally was used only for exported models, in the Soviet Union the same model was called Sputnik ("fellow traveler", "satellite") until 1991, when the sedan version of the Samara entered in production, using the export name. It was the first front-wheel drive serial car built in the Soviet Union after the LuAZ-969V. The Samara had been modified and restyled during the years of production before it was finally discontinued in December 2013.


title: Lada Samara

text: The Samara was a car that combined a robust build and ease of maintenance with a modern style. It was produced in various three, four and five-door designs with 1.1, 1.3 and 1.5-litre petrol engines. VAZ had hoped that the Samara would enable it to compete for sales in the mainstream European car market, where the company's traditional Fiat 124-based "Zhiguli" models were looked upon as increasingly outmoded and out of date. It was the second autonomous design from VAZ (the first was the Niva SUV), and the first model not based on the Fiat 124 mechanicals.


title: Lada Samara

text: VAZ had made their first front-wheel drive prototype, the VAZ-1101, in the early 1970s. The engine from the Fiat 127 was used. Further development of this project led to the "Ladoga" three-door hatchback prototype in 1976. The decision to build the Samara was taken on 16 September 1978, the intention being to build a car with strong potential sales in Western European export markets. Proposals for a distinctive saloon, four-door, and both three- and five-door hatchback were considered; it was decided instead the saloon should share the three-door hatchback's sheetmetal forward of the C-pillar. (Design work on the four-door went toward the VAZ-2110 instead.) During its development, VAZ designers paid careful attention to the contemporary Renault 9, Volkswagen Golf, Ford Escort Mark III, Opel Kadett, and Volvo 340, which would be the new VAZ-2108's main competitors. Front suspension was MacPherson struts, rear by torsion bar. It also had rack and pinion steering, another Soviet first.


title: Lada Samara

text: On 31 December 1979, the first VAZ-2108 prototype was completed. It strongly resembled the earlier Ladoga, and the VAZ-1106 saloon. While named "Sputnik" at home, it was more commonly known as the Vos'merka ("Eighth") after the last digit in the model code. The export version was named after the Samara River, a tributary to the Volga. The first cars left the production line on 18 December 1984. These, the three-door hatchbacks (the only model available at first), were powered by a belt-driven SOHC inline-four, and were fitted with a four-speed gearbox. The three-door was joined by a five-door, and by models with (a destroked version of the 1288) or (a bored-out 1288) engines. (The head was developed in co-operation with Porsche, though most Western observers assumed Porsche's involvement went beyond just engines, and the carburetors in connection with Solex.)


title: Lada Samara

text: In 1987, the model range was joined by the 21083, with a engine and five-speed gearbox, and the 21081, with a . The 1099 was an export-only variant. Top speeds were (1099), (1288) and (1499); fuel economy was (1099), (1288), or (1499). VAZ also debuted the 2109 five-door hatchback that year, also available with the , , and . In 1989, the 21099 saloon followed, which had a new bonnet, grille, wings, and -longer rear overhang, as well as an improved dashboard. The 21099's front-end styling was adopted on the 2109 in 1992 and the 2108 in 1994.


title: Lada Samara

text: A number of other minor alterations followed, including fuel-injected engines to meet emissions regulations in export markets. On the earlier Samaras the front clip had been a separate piece, surrounding the headlights. On the sedan version, the fenders go all the way up to the headlights and the lip of the bonnet dips between the headlights and meets the slimmer grille. Full production of the 21099 began in December 1990, with models 210993 (1288), 21099 (1499). The saloon, intended as a premium model compared to the hatchback, was given a distinctive branding in some export markets: Diva (Belgium), Sagona (France), Forma (Germany). Belgium also offered a locally built convertible. The 1.1 and 1.3 were eventually taken out of production, having already been withdrawn from export markets.


title: Lada Samara

text: A Wankel engined Samara three-door hatchback, the 2108–91, powered by a two-rotor VAZ-415 (with two rotors) was sold in Russia only, and only in very small numbers. With a five-speed gearbox, it was priced at 56,000 rubles. Due to severe reliability problems, this remained rare, most commonly bought by police and other agencies to use as a pursuit vehicle, for which its top speed was ideal; it was capable of in eight seconds. The subsequent 2109-91 five-door hatchback had the same VAZ-415 and gearbox.


title: Lada Samara

text: There was also a rear-engined Samara 4x4 rally car, also known as the NAMI 0290, built for the 1985 Soyuz Rally; it had permanent four-wheel drive and a Zhiguli-based engine, over the rear axle. It was nicknamed Appelsin ("orange", for its paint), and used ZAZ-1102 doors (though the body was mostly fiberglass, weighing only ) and still using factory Samara wheels.


title: Lada Samara

text: The 1987 mid-engined Samara-EVA had a turbocharged 16-valve engine (with electronic fuel injection) of ; a naturally-aspirated version produced . The only component left untouched was the original Zhuguli 2106 block.


title: Lada Samara

text: An even more powerful Samara S-Proto appeared in 1989, putting out . Most notably, the Samara T3 came seventh in class in the 1990 Paris-Dakar Rally and fifth in 1991, piloted by Jacky Ickx. The T3 did not contain many Samara parts however, using the Porsche 959's four-wheel drive system and a 3.6-litre Porsche flat-six. It was developed by French concessionaire Lada-Poch together with NAMI and the Tupolev aircraft factory. In the mid-1980s Lada developed its first ever convertible car on its own, then actually entering production and quickly exported to most European countries, called the Lada Natasha Cabriolet, a four-seater convertible that was based on the popular Samara 1300/1500 models with a manual opening and closing canvas roof. Also in some European car markets the LADA Niva 4X4 1600 cc engine was also available for both the Lada Natasha and Lada Samara cars during the 1990s.


title: Lada Samara

text: The Samara was sold all across the world, from Australia to Canada, in most European countries and throughout the COMECON sphere. The build quality of the Samara was better than that of most Eastern European models. In most nations, versions and equipments were decided on and installed by the dealers themselves. These local varieties ranged from decals and badges to the convertible conversions offered in Belgium and Germany. The Samara was often sold under other names as well, in particular the VAZ 21099 (Samara Sedan), which was sold as the Sagona (France, Canada, and Spain), Diva (Belgium and the Netherlands), Forma (Germany) and Sable (Australia and New Zealand).


title: Lada Samara

text: It was engineered in right-hand drive for the UK market, where it was sold from November 1987. It was sold there until VAZ withdrew from the UK market in July 1997, and was the most popular Lada model sold in the UK during the 23 years that the brand was sold there.


title: Lada Samara

text: In certain markets where the tax structure benefited diesels (such as France and the Benelux), the Samara was available with a 1.5-litre Peugeot diesel engine in 1995–97.


title: Lada Samara

text: With VAZ facing financial hardships in 1996–1997, exports began coming to a halt. The Lada Samara disappeared from Canada after the 1997 model year, leaving the Niva as the only Lada sold in Canada for the 1998 model year. Exports to Australia and Great Britain ended around the same time. The biggest problem was GM's reluctance to sell the fuel-injection kits necessary for exports, as they doubted VAZ's ability to pay. Faced with parts shortages, tax problems, and the chaos and criminality of Russia in the mid-nineties, export efforts languished and RHD production was no longer feasible.


title: Lada Samara

text: As a partial response to this situation, a higher-quality version for the European market, the Lada EuroSamara or Samara Baltic in some markets, was assembled in Finland at the Valmet Automotive plant in Uusikaupunki. Production started in mid-1996 and ended in July 1998, with 14,000 cars made from 85 per cent Russian parts.


title: Lada Samara

text: The United Kingdom had to wait nearly three years for the Samara to go on sale, after its launch in the USSR, but sales were reasonably strong when the first versions of the car left forecourts, in November 1987.


title: Lada Samara

text: In a road test conducted by "The Motor" magazine, it scored more than 5 points out of 10 in most aspects and was praised for having a remarkably extensive list of standard equipment, "impressive" engine, good visibility and performance for its price segment, lowered fuel consumption, being good at cornering and "tolerably quiet", but also received criticism for having a cheap-looking interior and plastic mouldings and being "very turbulent" on poor roads.


title: Lada Samara

text: The £4,795 price at introduction "was much less expensive" than the competing Peugeot 309 or Ford Escort 1300. The Samara remained on sale in the United Kingdom right up to 4 July 1997, when the decision was made to withdraw from Great Britain and most other export markets.


title: Lada Samara

text: In countries where ruggedness was more important, it was more successful, selling reasonably well in Canada, Australia, and Finland for instance.


title: Lada Samara

text: The attempt to appeal to a wider clientele failed; while an improvement over previous Ladas, the Samara's higher price pitched it against stiffer West European competition.


title: Lada Samara

text: By the time of the Samara's launch, the British small family car market was effectively split into two segments: The large mainstream market was dominated by mass-market manufacturers, such as Ford, Vauxhall, and Volkswagen. The budget market consisted of Eastern European and Far Eastern brands, such as Škoda, FSO, Hyundai, and Proton.


title: Lada Samara

text: The aging Samara came bottom of the annual 1996 and 1997 JD Power and Top Gear surveys in Great Britain. In countries where ruggedness was more important, it did manage some success, selling reasonably well in Canada, Australia, and Finland for instance.


title: Lada Samara

text: Initially sold as a three- or five-door hatchback with a 1.3 petrol engine, a 1.5 version became available in October 1988. Metallic paint became an option for the first time in November 1989 when the 1.5 SLX was launched. A new entry-level model arrived in July 1990 when the 1.1 petrol engine was added to the range (Select or L). An updated version of the Samara was launched in April 1991, with all new trim levels. This was followed by the introduction of the VAZ 21099 saloon version 15 months later. The saloon also became available as a sporty 1.5 "Juno" from July 1994, featuring alloy wheels, swoopy, ill-fitting sideskirts and a rear spoiler. A fuel injected engine became available on the 1.3 and 1.5 models in August 1996.