Leopold Zekeng

Effectiveness and safety of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine in HIV-1-infected adults in Cameroon: open-label multicentre trial

BACKGROUND Generic fixed-dose combinations have been prequalified by WHO to treat HIV-infected patients in resource-limited countries. Despite their widespread use they are, however, not yet recommended by some of the major donor agencies owing to scarcity of clinical data on effectiveness, safety, and quality. We aimed to assess these issues for one of the most frequently prescribed treatments in Africa, a generic fixed-dose combination of nevirapine, stavudine, and lamivudine. METHODS 60 patients were followed in an open-label, 24-week multicentre trial in Cameroon. All patients received one tablet of the fixed-dose combination drug twice daily. The primary outcome measure was the proportion of patients with viral load less than 400 copies per mL at the end of the study period, in an intention-to-treat analysis. FINDINGS At baseline, 92% of patients (n=55) had AIDS; median CD4 count was 118 cells per microL (IQR 78-167) and median plasma HIV-1 RNA was 104?736 copies per mL (40804-243787). The proportion of patients with undetectable viral load (<400 copies per mL) after 24 weeks of treatment was 80% (95% CI 68-89). Median (IQR) change in viral load was -3.1 log10 copies per mL (-2.5 to -3.6) and in CD4 count 83 cells per microL (40-178). The probability of remaining alive or free of new AIDS-defining events was 0.85 (95% CI 0.73-0.92). Frequency of disease progression was 32.0 (95% CI 16.6-61.5), severe adverse effects 17.8 (7.4-42.7), and genotypic resistance mutations 7.1 (1.8-28.4) per 100 person-years. Mean reported adherence rate was 99%. Median drug concentrations in tablets were 96% of expected values for nevirapine, 89% for stavudine, and 99% for lamivudine. INTERPRETATION Our findings lend support to use and funding of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine as first-line antiretroviral treatment in developing countries.

The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations.

Objectives: To estimate age- and sex-specific herpes simplex virus type-2 (HSV-2) prevalence in urban African adult populations and to identify factors associated with infection. Design and methods: Cross-sectional, population-based samples of about 2000 adults interviewed in each of the following cities: Cotonou, Benin; Yaoundé, Cameroon; Kisumu, Kenya and Ndola, Zambia. Consenting study participants were tested for HIV, HSV-2 and other sexually transmitted infections. Results: HSV-2 prevalence was over 50% among women and over 25% among men in Yaoundé, Kisumu and Ndola, with notably high rates of infection among young women in Kisumu and Ndola (39% and 23%, respectively, among women aged 15-19 years). The prevalence in Cotonou was lower (30% in women and 12% in men). Multivariate analysis showed that HSV-2 prevalence was significantly associated with older age, ever being married, and number of lifetime sexual partners, in almost all cities and both sexes. There was also a strong, consistent association with HIV infection. Among women, the adjusted odds ratios for the association between HSV-2 and HIV infections ranged from 4.0 [95% confidence interval (CI) = 2.0-8.0] in Kisumu to 5.5 (95% CI = 1.7-18) in Yaoundé, and those among men ranged from 4.6 (95% CI = 2.7-7.7) in Ndola to 7.9 (95% CI = 4.1-15) in Kisumu. Conclusions: HSV-2 infection is highly prevalent in these populations, even at young ages, and is strongly associated with HIV at an individual level. At a population level, HSV-2 prevalence was highest in Kisumu and Ndola, the cities with the highest HIV rates, although rates were also high among women in Yaoundé, where there are high rates of partner change but relatively little HIV infection. The high prevalence of both infections among young people underlines the need for education and counselling among adolescents.

Multicentre study on factors determining differences in rate of spread of HIV in sub-Saharan Africa: methods and prevalence of HIV infection

Objective: The objective of this study was to explore whether the differences in rate of spread of HIV in different regions in sub-Saharan Africa could be explained by differences in sexual behaviour and/or factors influencing the probability of HIV transmission during sexual intercourse. Methods: A cross-sectional, population-based study was conducted in two cities with a high HIV prevalence (Kisumu in Kenya and Ndola in Zambia) and two cities with a relatively low HIV prevalence (Cotonou in Benin and Yaoundé in Cameroon). In each of these cities, approximately 1000 men and 1000 women, aged 15-49 years, were randomly selected from the general population. Consenting men and women were interviewed and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection and trichomoniasis (the latter for women only). In addition, a survey was conducted on a random sample of 300 sex workers in each city. The research instruments, including the questionnaires and the laboratory procedures, were standardized to permit comparison of results. Results: The numbers of men interviewed were 1021 in Cotonou, 973 in Yaoundé, 829 in Kisumu, and 720 in Ndola. The corresponding figures for women were 1095, 1116, 1060 and 1130. In Yaoundé, Kisumu and Ndola, the response rates for men were lower than for women due to failure to make contact with eligible men. The proportion of eligible women who were interviewed was 86% in Yaoundé, and 89% in Kisumu and Ndola. In Yaoundé, 76% of eligible men were interviewed, along with 82% in Kisumu and 75% in Ndola. The prevalence of HIV infection in men was 3.3% in Cotonou, 4.1% in Yaoundé, 19.8% in Kisumu and 23.2% in Ndola. For women, the respective figures were 3.4, 7.8, 30.1 and 31.9%. The prevalence of HIV infection among women aged 15-19 years was 23.0% in Kisumu and 15.4% in Ndola. Among women in Kisumu who had their sexual debut 5 years before the interview, the prevalence of HIV infection was 46%; in Ndola, it was 59%. Among sex workers, the prevalence of HIV infection was 57.5% in Cotonou, 34.4% in Yaoundé, 74.7% in Kisumu and 68.7% in Ndola. Conclusions: The HIV prevalence rates in the general population confirmed our preliminary assessment of the level of HIV infection in the four cities, which was based on estimates of HIV prevalence from sentinel surveillance among pregnant women. The very high prevalence of HIV infection among young women in Kisumu and Ndola calls for urgent intervention.

Simplified strategy for detection of recombinant human immunodeficiency virus type 1 group M isolates by gag/env heteroduplex mobility assay

We developed a heteroduplex mobility assay in the gag gene (gag HMA) for the identification of group M subtypes A to H. The assay covers the region coding for amino acid 132 of p24 to amino acid 20 of p7 (according to human immunodeficiency virus type 1 [HIV-1] ELI, 460 bp). The gag HMA was compared with sequencing and phylogenetic analysis of an evaluation panel of 79 HIV-1 group M isolates isolated from infected individuals from different geographic regions. Application of gag HMA in combination with env HMA on 252 HIV-1- positive plasma samples from Bénin, Cameroon, Kenya, and Zambia revealed a high prevalence of a variety of intersubtype recombinants in Yaoundé, Cameroon (53.8%); Kisumu, Kenya (26.8%); and Cotonou, Bénin (41%); no recombinants were identified among the samples from Ndola, Zambia. The AG(IbNG) circulating recombinant form, as determined by gag HMA, was found to be the most common intersubtype recombinant in Yaoundé (39.4%) and Cotonou (38.5%). Using a one-tube reverse transcriptase PCR protocol, this gag HMA in combination with env HMA is a useful tool for rapidly monitoring the prevalence of the various genetic subtypes as well as of recombinants of HIV-1. Moreover, this technology can easily be applied in laboratories in developing countries.ABSTRACT We developed a heteroduplex mobility assay in the gaggene (gag HMA) for the identification of group M subtypes A to H. The assay covers the region coding for amino acid 132 of p24 to amino acid 20 of p7 (according to human immunodeficiency virus type 1 [HIV-1] ELI, 460 bp). Thegag HMA was compared with sequencing and phylogenetic analysis of an evaluation panel of 79 HIV-1 group M isolates isolated from infected individuals from different geographic regions. Application of gag HMA in combination with envHMA on 252 HIV-1- positive plasma samples from Bénin, Cameroon, Kenya, and Zambia revealed a high prevalence of a variety of intersubtype recombinants in Yaoundé, Cameroon (53.8%); Kisumu, Kenya (26.8%); and Cotonou, Bénin (41%); no recombinants were identified among the samples from Ndola, Zambia. The AGIbNG circulating recombinant form, as determined bygag HMA, was found to be the most common intersubtype recombinant in Yaoundé (39.4%) and Cotonou (38.5%). Using a one-tube reverse transcriptase PCR protocol, this gag HMA in combination with env HMA is a useful tool for rapidly monitoring the prevalence of the various genetic subtypes as well as of recombinants of HIV-1. Moreover, this technology can easily be applied in laboratories in developing countries.

Sensitivity of United States HIV antibody tests for detection of HIV-1 group O infections.

Infections by highly divergent strains of HIV-1, first detected in central Africa and grouped provisionally as group O, have not been reliably detected by certain European HIV screening tests. Serum specimens from eight probable group O infections from Cameroon were tested by ten HIV assays licensed by the US Food and Drug Administration. All assays based on synthetic peptides or recombinant antigens failed to detect at least one of the infections; assays based on whole-virus lysates performed better. Divergent HIV strains may be undetected by current HIV tests. Thus active surveillance for and characterisation of HIV variants to evaluate and, when necessary, modify current tests is urgently needed.

The multicentre study on factors determining the differential spread of HIV in four African cities: summary and conclusions

In all regions of sub-Saharan Africa the predominant mode of transmission of HIV is through heterosexual intercourse however there are large variations in the rate and extent of the spread of HIV in different populations. This study was conducted to identify the factors that influence the rapid spread of HIV in four African cities namely Cotonou (Benin) Yaounde (Cameroon) Kisumu (Kenya) and Ndola (Zambia). Results demonstrated that high rates of partner change and being married are risk factors for HIV infection in men in at least one city but are risk factors for women in all four cities. In addition condom use among sex workers did not show a difference between the low and high prevalence cities. Furthermore no evidence of changes towards safer sexual behavior was identified in the high HIV prevalence cities. The only factors that were more common in the two high HIV prevalence cities than in the two low HIV prevalence cities were young age at first intercourse for women young age at first marriage and large age difference between the spouses. It was also noted that the high levels of HIV infection among young people especially among female adolescents in Kisumu and Ndola highlight the importance of interventions targeted at young people and their partners.

Barrier contraceptive use and Hiv infection among high-risk women in Cameroon

ObjectivesTo measure the association between spermicide use and HIV infection, adjusting for condom use, and to measure the association between condom use and HIV infection, adjusting for spermicide use. DesignProspective study of women using nonoxynol-9 (N-9) spermicides and latex condoms, with up to 12 monthly clinic visits for interviews, examinations and tests, and re-supply. MethodsA total of 273 HIV-negative women with multiple sexual partners were enrolled, given latex condoms and N-9 vaginal spermicidal suppositories, and advised to use both every time they had sexual intercourse. Participants recorded data on sexual activity on pictorial coital logs. New HIV infections were detected and confirmed by quarterly enzyme-linked immunosorbent assays and Western blots, respectively. ResultsNineteen HIV infections occurred during mean follow-up of 8.1 months (an incidence rate of 10.4 infections per 100 woman-years). The adjusted HIV rate ratio (RR) was 0.1 [95% confidence interval (CI), 0.1–0.6] for more consistent compared with less consistent spermicide users; and 1.1 (95% Cl, 0.4–2.9) for more consistent compared with less consistent condom users. Among the subgroup of experienced condom users, the RR for more versus less consistent condom use was 0.3. ConclusionsThis is the first epidemiological evidence that N-9 spermicides can reduce the incidence of HIV infection. A more definitive randomized clinical trial is urgently needed.

Decreased Fertility Among HIV-1 Infected Women Attending Antenatal Clinics in Three African Cities

&NA;Population HIV prevalence estimates rely heavily on sentinel surveillance in antenatal clinics (ANCs), but because HIV reduces fertility, these estimates are biased. To aid interpretation of such data, we estimated HIV‐associated fertility reduction among pregnant women in ANCs in Yaoundé (Cameroon), Kisumu (Kenya), and Ndola (Zambia). Data collection followed existing HIV sentinel surveillance procedures as far as possible. HIV prevalence among the women was 5.5% in Yaoundé, 30.6% in Kisumu, and 27.3% in Ndola. The birth interval was prolonged in HIV‐positive multiparous women compared with HIV‐negative multiparous women in all three sites: adjusted hazard ratios of pregnancy were 0.84 (95% confidence interval [CI]: 0.62‐1.1) in Yaoundé, 0.82 (95% CI: 0.70‐0.96) in Kisumu, and 0.74 (95% CI: 0.61‐0.90) in Ndola, implying estimated reductions in the risk of pregnancy in HIV‐positive women of between 16% and 26%. For primiparous women, the interval between sexual debut and birth was longer in HIV‐positive women than in HIV‐negative women in all sites, although the association was lost in Ndola after adjusting for age and other factors. Consistent results in different study sites help in the development of standard methods for improving ANC‐based surveillance estimates of HIV prevalence. These may be easier to devise for multiparous women than for primiparous women.

Biological and genetic characteristics of HIV infections in Cameroon reveals dual group M and O infections and a correlation between SI-inducing phenotype of the predominant CRF02_AG variant and disease stage.

In Yaounde, Cameroon, HIV-1 group-specific V3 serology on 1469 HIV-positive samples collected between 1996 and 2001 revealed that group O infections remained constant around 1% for 6 years. Only one group N sample was identified and 4.3% reacted with group M and O peptides. Although the sensitivity of the group-specific polymerase chain reaction (PCR) in two genomic regions was not optimal, we confirmed, in at least 6 of 49 (12.2%) dual O/M seropositive samples and in 1 of 9 group O samples, dual infection with group O and M viruses (n = 4) or with group O or M virus and an intergroup recombinant virus (n = 3). Partial env (V3-V5) sequences on a subset of 295 samples showed that at least eight subtypes and five circulating recombinant forms (CRFs) of HIV-1 group M co-circulate; more than 60% were CRF02_AG and 11% had discordant subtype/CRF designations between env and gag. Similarly as for subtype B, the proportion of syncytium-inducing strains increased when CD4 counts were low in CRF02_AG-infected patients. The V3-loop charge was significantly lower for non-syncytium-inducing strains than for syncytium-inducing strains but cannot be used as an individual marker to predict phenotype. The two predominant HIV-1 variants in Africa, CRF02_AG and subtype C, thus have different biological characteristics.

Does increased general schooling protect against HIV infection? A study in four African cities

Background  The association between educational attainment and risk of HIV infection varies between populations and over time. Earlier studies in sub‐Saharan Africa have found that those with more education are at increased risk of HIV infection.