HIV seroprevalence, self-reported STIs and associated risk factors among men who have sex with men: a cross-sectional study in Rwanda, 2015.

OBJECTIVES: In many populations, men who have sex with men (MSM) are at a high risk of HIV infection. This study aimed to estimate the burden of HIV, other STIs and risk behaviours among Rwandan MSM. METHODS: In this cross-sectional study, we recruited through peer referral men aged between 18 and 60 years, who reported sex with men at least once in the 12 months prior to the survey. Representativeness was increased using 'seeds' from a variety of sources. Signed informed consent was obtained from all participants. Data on demographics, risk behaviours and self-reported STIs were collected through an interviewer-administered questionnaire. We screened all eligible participants for HIV using the Rwanda-approved protocol for rapid HIV detection. RESULTS: 504 MSM were recruited from five major cities in Rwanda. Participants were mostly young (median age 23 years, range 18-55 years) and unmarried (484/504, 96.0%). Thirteen per cent (65/504) of the participants reported past gonorrhoea and/or syphilis infection. Of 504 MSM, 53 (10.5%) reported they were diagnosed and treated for gonorrhoea in the past 12 months and 24 (4.8%) tested positive for HIV. A high proportion (232/504, 46%) reported receiving payment for sex by a man, with almost half of these reporting on more than three occasions (107/232, 46%). Many reported having had an HIV test within the past 12 months (385/504, 76.4%). In multivariate logistic regression models controlling for age, being paid for sex was associated with higher odds of past STI (OR 3.36 (1.82-6.43]; P<0.001) and testing HIV positive (OR 3.13, P<0.05). CONCLUSION: Further research is needed to understand the high rate of payment for sex in this population, which appears to be a major risk factor for STI including HIV.

HIV-1 Superinfection Resembles Primary Infection.

The relevance of superinfection as a model to identify correlates of protection against human immunodeficiency virus (HIV) depends on whether the superinfecting transmission resembles primary infection, which has not been established. Here, we characterize the genetic bottleneck in superinfected individuals for the first time. In all 3 cases, superinfection produced a spike in viral load and could be traced to a single, C-C chemokine receptor 5-tropic founder virus with shorter, less glycosylated variable regions than matched chronic viruses. These features are consistent with primary HIV transmission and provide support for the use of superinfection as a model to address correlates of protection against HIV.

In Utero Mother-to-Child Transmission of HIV-1 and the Associated Factors in Rwanda, Africa.

Mother-to-child transmission (MTCT) of HIV-1 and associated mortality continue to occur at unacceptably high rates, despite the extensive rollout and implementation of Prevention of Mother-to-Child Transmission (PMTCT) Programs, including the modified versions of Option B and B+ in 2010 and 2012, respectively. Maternal HIV viral load (VL) and socio-behavioral factors sustaining MTCT in Rwanda remain largely unexplored. The study examined the effects of socio-behavioral factors on maternal VL and their contribution to in utero transmission of HIV-1 in the context of Rwanda's HIV epidemic. A prospective cohort study was conducted in 862 mother-baby pairs enrolled in 10 PMTCT clinics in Rwanda. VL was determined on plasma and Dried Blood Spots samples, whereas HIV DNA PCR was performed to determine in utero MTCT of HIV of the babies immediately at birth and then at 3 weeks, 4 weeks, 6 months, and 18 months, together with HIV antibody testing to determine other forms of MTCT of HIV. Quantitative data on socio-behavioral factors were collected through a structured questionnaire. Linear regression and univariate analysis of variances using SPSS 25.0 were used to test the hypotheses. We found 22/862 (2.55%) cases of in utero transmission and a total of 32/862 (3.7%) cases of MTCT of HIV-1 over 18 study months. Maternal VL at delivery was significantly associated with the risk of in utero transmission of HIV-1. Socio-behavioral factors associated with elevated maternal VL at delivery included alcohol, smoking, multiple sexual partners, mothers' income, being a casual laborer, and distance to health care services. We report an MTCT rate of 3.7% in our study population over the 18 months, higher than the national average of 1.5%, the majority of which occurred in utero. MTCT cases were attributable to failure to suppress maternal VL.

Intersubtype differences in the effect of a rare p24 gag mutation on HIV-1 replicative fitness.

Certain immune-driven mutations in HIV-1, such as those arising in p24(Gag), decrease viral replicative capacity. However, the intersubtype differences in the replicative consequences of such mutations have not been explored. In HIV-1 subtype B, the p24(Gag) M250I mutation is a rare variant (0.6%) that is enriched among elite controllers (7.2%) (P = 0.0005) and appears to be a rare escape variant selected by HLA-B58 supertype alleles (P < 0.01). In contrast, in subtype C, it is a relatively common minor polymorphic variant (10 to 15%) whose appearance is not associated with a particular HLA allele. Using site-directed mutant viruses, we demonstrate that M250I reduces in vitro viral replicative capacity in both subtype B and subtype C sequences. However, whereas in subtype C downstream compensatory mutations at p24(Gag) codons 252 and 260 reduce the adverse effects of M250I, fitness costs in subtype B appear difficult to restore. Indeed, patient-derived subtype B sequences harboring M250I exhibited in vitro replicative defects, while those from subtype C did not. The structural implications of M250I were predicted by protein modeling to be greater in subtype B versus C, providing a potential explanation for its lower frequency and enhanced replicative defects in subtype B. In addition to accounting for genetic differences between HIV-1 subtypes, the design of cytotoxic-T-lymphocyte-based vaccines may need to account for differential effects of host-driven viral evolution on viral fitness.

Fluidity of HIV-1-specific T-cell responses during acute and early subtype C HIV-1 infection and associations with early disease progression.

Deciphering immune events during early stages of human immunodeficiency virus type 1 (HIV-1) infection is critical for understanding the course of disease. We characterized the hierarchy of HIV-1-specific T-cell gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay responses during acute subtype C infection in 53 individuals and associated temporal patterns of responses with disease progression in the first 12 months. There was a diverse pattern of T-cell recognition across the proteome, with the recognition of Nef being immunodominant as early as 3 weeks postinfection. Over the first 6 months, we found that there was a 23% chance of an increased response to Nef for every week postinfection (P = 0.0024), followed by a nonsignificant increase to Pol (4.6%) and Gag (3.2%). Responses to Env and regulatory proteins appeared to remain stable. Three temporal patterns of HIV-specific T-cell responses could be distinguished: persistent, lost, or new. The proportion of persistent T-cell responses was significantly lower (P = 0.0037) in individuals defined as rapid progressors than in those progressing slowly and who controlled viremia. Almost 90% of lost T-cell responses were coincidental with autologous viral epitope escape. Regression analysis between the time to fixed viral escape and lost T-cell responses (r = 0.61; P = 0.019) showed a mean delay of 14 weeks after viral escape. Collectively, T-cell epitope recognition is not a static event, and temporal patterns of IFN-γ-based responses exist. This is due partly to viral sequence variation but also to the recognition of invariant viral epitopes that leads to waves of persistent T-cell immunity, which appears to associate with slower disease progression in the first year of infection.

Early evolution of human leucocyte antigen-associated escape mutations in variable Gag proteins predicts CD4+ decline in HIV-1 subtype C-infected women.

OBJECTIVE: HIV-1 escape from cytotoxic T-lymphocytes results in the accumulation of human leucocyte antigen (HLA)-associated mutations in the viral genome. To understand the contribution of early escape to disease progression, this study investigated the evolution and pathogenic implications of cytotoxic T-lymphocyte escape in a cohort followed from infection for 5 years. METHODS: Viral loads and CD4 cell counts were monitored in 78 subtype C-infected individuals from onset of infection until CD4 cell count decline to less than 350 cells/µl or 5 years postinfection. The gag gene was sequenced and HLA-associated changes between enrolment and 12 months postinfection were mapped. RESULTS: HLA-associated escape mutations were identified in 48 (62%) of the participants and were associated with CD4 decline to less than 350 cells/µl (P = 0.05). Escape mutations in variable Gag proteins (p17 and p7p6) had a greater impact on disease progression than escape in more conserved regions (p24) (P = 0.03). The association between HLA-associated escape mutations and CD4 decline was independent of protective HLA allele (B57, B58 : 01 and B81) expression. CONCLUSION: The high frequency of escape contributed to rapid disease progression in this cohort. Although HLA-adaption in both conserved and variable Gag domains in the first year of infection was detrimental to long-term clinical outcome, escape in variable domains had greater impact.