Etienne Karita

New heterosexually transmitted HIV infections in married or cohabiting couples in urban Zambia and Rwanda: an analysis of survey and clinical data

BACKGROUND Sub-Saharan Africa has a high rate of HIV infection, most of which is attributable to heterosexual transmission. Few attempts have been made to assess the extent of HIV transmission within marriages, and HIV-prevention efforts remain focused on abstinence and non-marital sex. We aimed to estimate the proportion of heterosexual transmission of HIV which occurs within married or cohabiting couples in urban Zambia and Rwanda each year. METHODS We used population-based data from Demographic and Health Surveys (DHS) on heterosexual behaviour in Zambia in 2001-02 and in Rwanda in 2005. We also used data on the HIV serostatus of married or cohabiting couples and non-cohabiting couples that was collected through a voluntary counselling and testing service for urban couples in Lusaka, in Zambia, and Kigali, in Rwanda. We estimated the probability that an individual would acquire an incident HIV infection from a cohabiting or non-cohabiting sexual partner, and then the proportion of total heterosexual HIV transmission which occurs within married or cohabiting couples in these settings each year. FINDINGS We analysed DHS data from 1739 Zambian women, 540 Zambian men, 1176 Rwandan women, and 606 Rwandan men. Under our base model, we estimated that 55.1% to 92.7% of new heterosexually acquired HIV infections among adults in urban Zambia and Rwanda occurred within serodiscordant marital or cohabiting relationships, depending on the sex of the index partner and on location. Under our extended model, which incorporated the higher rates of reported condom use that we found with non-cohabiting partners, we estimated that 60.3% to 94.2% of new heterosexually acquired infections occurred within marriage or cohabitation. We estimated that an intervention for couples which reduced transmission in serodiscordant urban cohabiting couples from 20% to 7% every year could avert 35.7% to 60.3% of heterosexually transmitted HIV infections that would otherwise occur. INTERPRETATION Since most heterosexual HIV transmission for both men and women in urban Zambia and Rwanda takes place within marriage or cohabitation, voluntary counselling and testing for couples should be promoted, as should other evidence-based interventions that target heterosexual couples.

Human Immunodeficiency Virus Type 1 Elite Neutralizers: Individuals with Broad and Potent Neutralizing Activity Identified by Using a High-Throughput Neutralization Assay together with an Analytical Selection Algorithm

ABSTRACT The development of a rapid and efficient system to identify human immunodeficiency virus type 1 (HIV-1)-infected individuals with broad and potent HIV-1-specific neutralizing antibody responses is an important step toward the discovery of critical neutralization targets for rational AIDS vaccine design. In this study, samples from HIV-1-infected volunteers from diverse epidemiological regions were screened for neutralization responses using pseudovirus panels composed of clades A, B, C, and D and circulating recombinant forms (CRFs). Initially, 463 serum and plasma samples from Australia, Rwanda, Uganda, the United Kingdom, and Zambia were screened to explore neutralization patterns and selection ranking algorithms. Samples were identified that neutralized representative isolates from at least four clade/CRF groups with titers above prespecified thresholds and ranked based on a weighted average of their log-transformed neutralization titers. Linear regression methods selected a five-pseudovirus subset, representing clades A, B, and C and one CRF01_AE, that could identify top-ranking samples with 50% inhibitory concentration (IC50) neutralization titers of ≥100 to multiple isolates within at least four clade groups. This reduced panel was then used to screen 1,234 new samples from the Ivory Coast, Kenya, South Africa, Thailand, and the United States, and 1% were identified as elite neutralizers. Elite activity is defined as the ability to neutralize, on average, more than one pseudovirus at an IC50 titer of 300 within a clade group and across at least four clade groups. These elite neutralizers provide promising starting material for the isolation of broadly neutralizing monoclonal antibodies to assist in HIV-1 vaccine design.

Postnatal transmission of human immunodeficiency virus type 1 from mother to infant -- a prospective cohort study in Kigali Rwanda.

Abstract Background. Although transmission of human immunodeficiency virus type 1 (HIV-1 ) from mother to infant has been well documented during pregnancy and delivery, little is known about the possible transmission of HIV-1 during the postnatal period. Methods. We conducted a prospective cohort study in Kigali, Rwanda, of 212 mother—infant pairs who were seronegative for HIV-1 at delivery. All the infants were breast-fed. The subjects were followed at three-month intervals, with Western blot assays for antibodies to HIV-1 and testing of mononuclear cells by a double polymerase chain reaction (PCR) using three sets of primers. To evaluate potential risk factors, each mother who seroconverted was matched with three seronegative control women. Results. After a mean follow-up of 16.6 months, 16 of the 212 mothers became seropositive for HIV-1. Of their 16 infants, 9 became seropositive. One infant was excluded from the analysis because of a positive test by PCR on the blood sample obtained at birth. Postnat...

Inflammatory Genital Infections Mitigate a Severe Genetic Bottleneck in Heterosexual Transmission of Subtype A and C HIV-1

The HIV-1 epidemic in sub-Saharan Africa is driven largely by heterosexual transmission of non-subtype B viruses, of which subtypes C and A are predominant. Previous studies of subtype B and subtype C transmission pairs have suggested that a single variant from the chronically infected partner can establish infection in their newly infected partner. However, in subtype A infected individuals from a sex worker cohort and subtype B individuals from STD clinics, infection was frequently established by multiple variants. This study examined over 1750 single-genome amplified viral sequences derived from epidemiologically linked subtype C and subtype A transmission pairs very early after infection. In 90% (18/20) of the pairs, HIV-1 infection is initiated by a single viral variant that is derived from the quasispecies of the transmitting partner. In addition, the virus initiating infection in individuals who were infected by someone other than their spouse was characterized to determine if genital infections mitigated the severe genetic bottleneck observed in a majority of epidemiologically linked heterosexual HIV-1 transmission events. In nearly 50% (3/7) of individuals infected by someone other than their spouse, multiple genetic variants from a single individual established infection. A statistically significant association was observed between infection by multiple genetic variants and an inflammatory genital infection in the newly infected individual. Thus, in the vast majority of HIV-1 transmission events in cohabiting heterosexual couples, a single genetic variant establishes infection. Nevertheless, this severe genetic bottleneck can be mitigated by the presence of inflammatory genital infections in the at risk partner, suggesting that this restriction on genetic diversity is imposed in large part by the mucosal barrier.

HLA class I homozygosity accelerates disease progression in human immunodeficiency virus type 1 infection

Polymorphic products of HLA class I genes restrict cytotoxic T lymphocyte responses to the constantly evolving spectrum of HIV-1 antigens. Accordingly, homozygosity at class I loci can reduce the repertoire for such HLA-dependent interactions, leading to accelerated disease progression. To test this hypothesis we studied subjects from two distinct HIV/AIDS cohorts: 140 Dutch homosexual men and 202 Rwandan heterosexual women followed up to 13 years from HIV-1 seroconversion. We performed intermediate- and selective high-resolution molecular typing at HLA class I (A, B, and C) and high-resolution typing at HLA class II DRB1 and DQB1. Homozygosity at the HLA-A or -B locus or both was found at increasingly high frequency among individuals with successively more rapid progression to late-stage HIV-1-related conditions. In the combined cohorts (n = 342) the odds ratio (OR) due to HLA-A or -B antigen homozygosity in rapid versus slow progressors was 3.8 (p = 0.003); for Dutch men alone the OR was 3.5 (p = 0.102), and for Rwandan women the OR was 4.1 (p = 0.009). In contrast, homozygous genotypes at either HLA-C, DRB1, or DQB1 alone, or DRB1-DQB1 haplotypes, did not exert any deleterious effect on HIV-1 disease progression. These findings suggest strongly that diversity in addition to sequence specificity at HLA-A and -B loci can influence the rate of disease progression following HIV-1 infection.

Natural History of Human Immunodefiency Virus Type 1 Infection in Children: A Five-Year Prospective Study in Rwanda

Objective. To compare morbidity and mortality of human immunodeficiency virus type 1 (HIV-1)-infected and HIV-1-uninfected children and to identify predictors of acquired immunodeficiency syndrome (AIDS) and death among HIV-1-infected children in the context of a developing country. Design. Prospective cohort study. Setting. Maternal and child health clinic of the Centre Hospitalier de Kigali, Rwanda. Participants. Two hundred eighteen children born to HIV-1-seropositive mothers and 218 born to seronegative mothers of the same age and parity were enrolled at birth. Outcome Measures. Deaths, clinical AIDS, nonspecific HIV-related manifestations, and use of health care services. Results. Fifty-four infected and 347 uninfected children were followed up for a median of 27 and 51 months, respectively. With the exception of chronic cough, the risk of occurrence of nonspecific HIV-related conditions was 3 to 13 times higher in infected than in uninfected children. The recurrence rate and severity of these findings were increased systematically in infected infants. Estimated cumulative risk of developing AIDS was 28% and 35% at 2 and 5 years of age, respectively. Estimated risk of death among infected children at 2 and 5 years of age was 45% and 62%, respectively, a rate 21 times higher than in uninfected children. Median survival time after estimated infection was 12.4 months. Early infection, early onset of HIV-related conditions, failure to thrive, and generalized lymphadenopathy were associated with subsequent risk of death and/or AIDS, whereas lymphoid interstitial pneumonitis was predictive of a milder disease. Conclusions. In Africa, HIV-1-infected children develop disease manifestations early in life. Specific clinical findings are predictive of HIV-1 disease, AIDS stage, and death. Bimodal expression of HIV-1 pediatric disease is encountered in Africa, as in industrialized countries, but prognosis is poorer. human immunodeficiency virus infection, children, vertical transmission, natural history, Africa.

Sexual practices of HIV discordant and concordant couples in Rwanda: effects of a testing and counselling programme for men:

As part of a longitudinal investigation, the husbands and cohabiting male partners of 684 Rwandan women were recruited to participate in an HIV testing and counselling programme. All of the women and 256 of the men (37%) had previously received standard testing and generic counselling services. In this project, all of the men participated in an extensive, male-focused counselling programme. This included 428 men who were receiving testing and counselling for the first time. Interview responses indicated that rates of condom use during sexual intercourse increased dramatically at the one-year follow-up assessment for the serodiscordant couples. This effect was especially strong for couples whose male partners were receiving testing and counselling for the first time. Rates of condom use also increased substantially in seroconcordant HIV-positive couples whose partners had both been tested previously. Women in couples with at least one seropositive partner reported lower rates of coercive sex by their male partners after they completed the counselling programme. Male-focused and couple-focused testing and counselling programmes appear to be effective in reducing risky sexual behaviours in heterosexual couples, even if one or both partners have received testing and counselling services previously.

Time from HIV seroconversion to death: a collaborative analysis of eight studies in six low and middle-income countries before highly active antiretroviral therapy.

Objectives:To estimate survival patterns after HIV infection in adults in low and middle-income countries. Design:An analysis of pooled data from eight different studies in six countries. Methods:HIV seroconverters were included from eight studies (three population-based, two occupational, and three clinic cohorts) if they were at least 15 years of age, and had no more than 4 years between the last HIV-negative and subsequent HIV-positive test. Four strata were defined: East African cohorts; South African miners cohort; Thai cohorts; Haitian clinic cohort. Kaplan–Meier functions were used to estimate survival patterns, and Weibull distributions were used to model and extend survival estimates. Analyses examined the effect of site, age, and sex on survival. Results:From 3823 eligible seroconverters, 1079 deaths were observed in 19 671 person-years of follow-up. Survival times varied by age and by study site. Adjusting to age 25–29 years at seroconversion, the median survival was longer in South African miners: 11.6 years [95% confidence interval (CI) 9.8–13.7] and East African cohorts: 11.1 years (95% CI 8.7–14.2) than in Haiti: 8.3 years (95% CI 3.2–21.4) and Thailand: 7.5 years (95% CI 5.4–10.4). Survival was similar for men and women, after adjustment for age at seroconversion and site. Conclusion:Without antiretroviral therapy, overall survival after HIV infection in African cohorts was similar to survival in high-income countries, with a similar pattern of faster progression at older ages at seroconversion. Survival appears to be significantly worse in Thailand where other, unmeasured factors may affect progression.

Investigating the utility of the HIV-1 BED capture enzyme immunoassay using cross-sectional and longitudinal seroconverter specimens from Africa.

Background:The identification of populations at risk of HIV infection is a priority for trials of preventive technologies, including HIV vaccines. To quantify incidence traditionally requires laborious and expensive prospective studies. Methods:The BED IgG–Capture enzyme immunoassay (EIA) was developed to estimate HIV-1 incidence using cross-sectional data by measuring increasing levels of HIV-specific IgG as a proportion of total IgG. To evaluate this assay, we tested 189 seroconversion samples taken at 3-monthly intervals from 15 Rwandan and 26 Zambian volunteers with known time of infection and cross-sectional specimens from 617 Kenyan and Ugandan volunteers with prevalent infection. Results:The BED–EIA-estimated incidence in Uganda was unexpectedly high, at 6.1%/year [95% confidence interval (CI) 4.2–8.0] in Masaka and 6.0%/year (95% CI 4.3–7.7) in Kakira. Prospective incidence data in Masaka from the same population was 1.7%/year before and 1.4%/year after the study. Kenyan estimates were 3.5%/year in Kilifi (95% CI 2.1–4.9) and 3.4%/year in Nairobi (95% CI 1.5–5.3). From the Rwandan and Zambian data, the sensitivity of the assay was 81.2% and the specificity was 67.8%. After approximately one year, subjects misclassified as recently infected tended to have lower plasma viral loads compared with those not misclassified as recent (median copies/ml 14 773 versus 93 560; P = 0.02). Clinical presentation, sex and HIV subtype were not significantly associated with BED–EIA misclassification in seroconverter samples. Conclusion:These data suggest that this assay does not perform reliably in all populations. Further research is warranted before using this assay to estimate incidence from prevalent HIV samples.

Access to adequate nutrition is a major potential obstacle to antiretroviral adherence among HIV-infected individuals in Rwanda.

Despite the massive expansion of antiretroviral drugs in Africa, little is known about the resulting changes in sexual behavior or obstacles to antiretroviral therapy (ART) adherence. Our evaluation of Rwandan adults on ART found no increase in risky sexual behaviors, but an obstacle to ART initiation and adherence for 76% of patients was a fear of developing too much appetite without enough to eat. Access to adequate nutrition may be a major determinant for long-term adherence to ART.